modulo: Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References
Gene name - modulo

Synonyms -

Cytological map position - 100E3

Function - Transcription factor, RNA binding protein

Keywords - modifier of PEV, cellular growth rate

Symbol - mod

FlyBase ID: FBgn0002780

Genetic map position - 3R

Classification - RRM-containing domain

Cellular location - nuclear



NCBI link: Entrez Gene
mod orthologs: Biolitmine
Recent literature
Falahati, H. and Wieschaus, E. (2017). Independent active and thermodynamic processes govern the nucleolus assembly in vivo. Proc Natl Acad Sci U S A 114(6): 1335-1340. PubMed ID: 28115706
Summary:
Membraneless organelles play a central role in the organization of protoplasm by concentrating macromolecules, which allows efficient cellular processes. Recent studies have shown that, in vitro, certain components in such organelles can assemble through phase separation. Inside the cell, however, such organelles are multicomponent, with numerous intermolecular interactions that can potentially affect the demixing properties of individual components. In addition, the organelles themselves are inherently active, and it is not clear how the active, energy-consuming processes that occur constantly within such organelles affect the phase separation behavior of the constituent macromolecules. This study examined the phase separation model for the formation of membraneless organelles in vivo by assessing the two features that collectively distinguish it from active assembly, namely temperature dependence and reversibility. A microfluidic device that allows accurate and rapid manipulation of temperature was used, and the quantitative dynamics were examined by which six different nucleolar proteins (Modulo, Fibrillarin, Nucleostemin1, Pitchoune, Nopp140 and Ppl135) assemble into the nucleoli of Drosophila melanogaster embryos. The results indicate that, although phase separation is the main mode of recruitment for four of the studied proteins, the assembly of the other two is irreversible and enhanced at higher temperatures, behaviors indicative of active recruitment to the nucleolus. These two subsets of components differ in their requirements for ribosomal DNA; the two actively assembling components fail to assemble in the absence of ribosomal DNA, whereas the thermodynamically driven components assemble but lose temporal and spatial precision.
Jiang, M., Gao, Z., Wang, J. and Nurminsky, D. I. (2018). Evidence for a hierarchical transcriptional circuit in Drosophila male germline involving testis-specific TAF and two gene-specific transcription factors, Mod and Acj6. . FEBS Lett 592(1): 46-59. PubMed ID: 29235675
Summary:
To analyze transcription factors involved in gene regulation by testis-specific TAF (tTAF see Cannonball), tTAF-dependent promoters were mapped and analyzed in silico. Core promoters show decreased AT content, paucity of classical promoter motifs, and enrichment with translation control element CAAAATTY. Scanning of putative regulatory regions for known position frequency matrices identified 19 transcription regulators possibly contributing to tTAF-driven gene expression. Decreased male fertility associated with mutation in one of the regulators, Acj6, indicates its involvement in male reproduction. Transcriptome study of testes from male mutants for tTAF, Acj6, and previously characterized tTAF-interacting factor Modulo implies the existence of a regulatory hierarchy of tTAF, Modulo and Acj6, in which Modulo and/or Acj6 regulate one-third of tTAF-dependent genes.
BIOLOGICAL OVERVIEW

The Drosophila modulo gene (mod) was first characterized as a dominant suppressor of Position effect variegation (PEV) (Garzino, 1992). PEV occurs in experimental strains where genes placed close to constitutive heterochromatin are randomly turned on or off, leading to mosaic adult structures. The products of genes that modify PEV are believed to change the local chromatin structure, which leads, when they are mutated, to an increased (suppression of variegation) or a decreased (enhancement of variegation) expression of neighboring genes. The dominant PEV suppression phenotype of mod, therefore, suggests that its product participates in the formation of multimeric protein complexes that package the DNA, promoting chromatin compaction and inactivation. mod, apart from its role in chromatin structuration, has a second cellular function and is required in nucleolus activity and protein synthesis capacity (Perrin, 1998). Cell clones deficient for mod express phenotypic traits characteristic of Minute mutations. The Modulo protein, while actually associated with condensed chromatin and heterochromatin sites, is also found abundantly at the nucleolus. Consistent with this localization, Mod displays a modular organization that is often found in nonribosomal nucleolar proteins (including an acidic stretch), two basic regions located at both ends of the molecule, and four reiterated RRMs in the remaining core portion (Perrin, 1999).

CREB-binding protein, dCBP, may regulate the formation of chromatin states through interactions with Modulo. dCBP and Modulo bind in vitro and in vivo, mutations in mod enhance the embryonic phenotype of a dCBP mutation, and dCBP mutations enhance the melanotic tumor phenotype characteristic of mod homozygous mutants. These results imply that, in addition to its histone acetyltransferase activity, dCBP may affect higher-order chromatin structure (Bantignies, 2002).

In gain of function and loss of function experiments, mod has been demonstrated to be directly controlled by dMyc. Strikingly, in proliferative imaginal cells, mod loss-of-function impairs both cell growth and cell size, whereas larval endoreplicative tissues grow normally. In contrast to dMyc, over-expressing Mod in wing imaginal discs is not sufficient to induce cell growth. Taken together, these results indicate that mod does not possess the full spectrum of dMyc activities, but is required selectively in proliferative cells to sustain their growth and to maintain their specific size (Perrin, 2003).

Mod is involved in distinct networks at nucleolus and chromatin and phosphorylation down-regulates DNA-binding and therefore controls distribution and function of Mod in the two sub-nuclear compartments. Structure/function analysis performed using Mod truncated isoforms has clearly identified the domains involved in nucleic-acid binding. One major conclusion is that Mod is a sequence/motif-specific RNA binding protein. Two lines of evidence indicate that this property is provided by the RRM-containing domain: (1) the same consensus was derived from SELEX experiments performed with GST fusions of either the whole protein or the RRM moiety only; (2) the two protein variants show close binding constant for association to selected RNAs. Structural probing and footprinting experiments predict that Mod stabilizes a hairpin-like structure and presumably establishes direct contacts within two single-stranded GU(A/G)G(U/A) and UUAC sequences corresponding to the hairpin loop and part of a bulged loop and with the ribose-phosphate backbone as well. This RNA motif appears quite different from that of the few targets of RRM-containing proteins identified so far -- these usually constitute hairpin loops of 8 to 10 residues. More generally, a search in data bases failed to reveal any significant resemblance between the Mod cognate motif and a previously identified RNA sequence. A second conclusion is that the two basic terminal domains of Mod are able to bind DNA in a non-sequence-specific manner. The decreased affinity of protein variants truncated of either the N or C terminus indicates that each domain can act independently. It is, however, conceivable that the two domains function synergistically in the native protein to improve DNA-binding activity (Perrin, 2003).

Mod therefore presents unique in vitro nucleic acid binding properties since it is able to directly contact DNA via the two tips and bind to a specific RNA motif via the central RRM domain. This led to a considertion of three points regarding the situation in vivo. One can first wonder about the nature of the nucleic acids Mod is interacting with at the nucleolus and chromatin. Clear evidence that Mod is released from the nucleolus as a RNP complex is provided by the RNase-induced modification of nucleosoluble Mod migration in native gel electrophoresis. Also consistent with a direct interaction with a nucleolar RNA, M12 aptamer (selected RNA sequence) specifically displaces the protein from the RNP complex. This latter result in addition strongly suggests that the Mod RNA target at nucleolus likely presents a structure similar to M12. However, no motif related to the aptamer in the repertoire of Drosophila rRNA or snoRNA sequences available in data bases has been found. Eukaryotic cells contain an extraordinarily complex population of snoRNAs, but only a few have been cloned in Drosophila. It is therefore tempting to assume that the Mod RNA target at the nucleolus corresponds to snoRNA sequences not identified so far. Since Mod does not to bind rDNA, it is concluded that in this compartment Mod associates to specific RNA molecule(s) but does not contact DNA. Interactions of Mod with nucleic acids at chromatin appear to be quite different. It is well established that the protein directly contacts genomic DNA (Garzino, 1992, Perrin, 1998). With respect to Mod's RNA-binding activity, digestion by RNase does not affect the Mod pattern on polytene chromosomes, while RNase induces efficient release of Male lethal from the X chromosome and of Mod from the nucleolus. The simplest explanation is that chromatin-associated Mod does not interact with RNA. Alternatively, in the process of chromatin compaction, Mod may recruit RNA together with additional protein factors to form highly condensed structures in which the RNA moiety is protected from digestion by RNase. Whether or not Mod requires a RNA partner in the process of chromatin compaction obviously needs further investigation (Perrin, 1999).

Regarding the molecular mechanisms that control Mod distribution between the two subnuclear compartments. It is proposed that posttranslational modification by phosphorylation down-regulates the DNA-binding activity and capacity of the protein to link chromatin and, therefore, modulates the equilibrium between chromatin versus nucleolus association. This model is supported by several lines of evidence: (1) the chromatin-bound protein does not detectably incorporate 32P in cell culture assays; (2) the nucleolar fraction is highly modified and cannot bind DNA in vitro; and (3) the DNA-binding activity is restored after digestion by phosphatase. In contrast, phosphorylation is unlikely to affect the capability of Mod to bind RNA because competition experiments have shown that the M12 aptamer, selected by a recombinant protein produced in E. coli (i.e., unmodified), binds phosphorylated nucleolar Mod as well (Perrin, 1999).

Another point to consider is how the molecular data correlate to, and possibly improve understanding of, functional data obtained from genetics. The dominant suppression of PEV phenotype unambiguously indicates that the encoded protein participates in the local assembly of high order chromatin structure and transcriptional silencing of neighboring genes. This function is thus clearly related to chromatin rather than nucleolus and to the DNA-binding activity of Mod. The lack of sequence specificity in DNA recognition that is exhibited by the two basic terminal domains in vitro contrasts with the protein distribution at specific heterochromatic sites on mitotic chromosomes (Perrin, 1998). This suggests that Mod might associate to unknown factors that could provide specificity and direct the complex toward particular chromatin sites. An interesting possibility is that the distal domains in Mod interact with sequences lying relatively far apart from each other on the DNA fiber, which could favor and stabilize the formation of condensed chromatin structures (Perrin, 1999).

Total loss of mod function results in the expression of several recessive phenotypes. Some have clearly been related to defects in ribosome biogenesis and protein synthesis capacity, such as the 'Minute-like' phenotype of mutant cell clones induced in a wild type background (Perrin, 1998) and defect in cell growth and proliferation of mutant imaginal tissues (Perrin, 1999).

Other phenotypes, melanotic tumor formation (Garzino, 1992) and lymph gland hyperplasia, which are highly reminiscent to phenotypes caused by mutations in the ribosomal protein S6 gene, are also consistent with a role for Mod in the regulation of ribosome assembly and cell growth. With respect to the melanotic tumor formation, it has been found that when associated with Modulo, dCBP can affect the immune response needed to suppress the formation of melanotic tumors in fly larvae (Bantignies, 2002). With respect to cell growth, it is clear that Mod carries out this function as a target of dMyc (Perrin, 2003). Interestingly, Mod phosphorylation is enhanced when cell growth is stimulated in cultures supplemented with serum. Since bidimensional gel analysis reveals a multiplicity of Mod phosphoisoforms in vivo, it is therefore tempting to assume that modification by phosphorylation at critical sites in Mod is required not only to prevent DNA-binding and chromatin compaction, but also to enhance nucleolus activity. Regarding the molecular function of Mod at the nucleolus, an involvement in rDNA transcription appears unlikely since the protein does not bind rDNA and is released from the organelle by low salt extraction of purified nuclei. Instead, it presumably participates in a subsequent step of the ribosome biosynthesis. Like most nucleolar proteins identified so far, Mod indeed presents a modular structure that combines four RRMs with acidic and basic domains and suggests interaction with nucleolar components, including ribosomal proteins, rRNA and/or snoRNAs, and possibly a chaperone function facilitating ribosome assembly (Perrin, 1999).


GENE STRUCTURE

cDNA clone length - 2275 bp

Bases in 5' UTR - 436

Exons - 6

Bases in 3' UTR - 210


PROTEIN STRUCTURE

Amino Acids - 542

Structural Domains

Following an immunological screen of an expression library, five cDNA clones have been isolated encoding the Modulo antigen, a DNA-binding protein differentially expressed during Drosophila development. In addition a series of overlapping cDNA and genomic clones were also isolated. This protein is the product of a 2.2 kb mRNA that is encoded by a single genetic locus (100F). Analysis of the complete 542 amino-acid sequence, deduced from nucleotide sequence of cDNAs, shows that the polypeptide exhibits a primary structure with distinct charged regions, a modular structure found in several eukaryotic nuclear proteins. The amino and carboxyl termini are rich in basic residues. The first third of the sequence contains a long domain comprised almost entirely of glutamic and aspartic acid residues. A typical cAMP dependent phosphorylation site and five potential glycosylation sites have been detected in the amino-acid sequence (Krejci, 1989).


EVOLUTIONARY HOMOLOGS

Nucleolin is one of the most abundant non-ribosomal proteins of the nucleolus. Several studies in vitro have shown that nucleolin is involved in several steps of ribosome biogenesis, including the regulation of rDNA transcription, rRNA processing, and ribosome assembly. However, the different steps of ribosome biogenesis are highly coordinated, and therefore it is not clear to what extent nucleolin is involved in each of these steps. It has been proposed that the interaction of nucleolin with the rDNA sequence and with nascent pre-rRNA leads to the blocking of RNA polymerase I (RNA pol I) transcription. To test this model and to get molecular insights into the role of nucleolin in RNA pol I transcription, the function of nucleolin was studied in Xenopus oocytes. Injection of a 2-4-fold excess of Xenopus or hamster nucleolin in stage VI Xenopus oocytes reduces the accumulation of 40 S pre-rRNA 3-fold, whereas transcription by RNA polymerase II and III is not affected. Direct analysis of rDNA transcription units by electron microscopy reveals that the number of polymerase complexes/rDNA unit is drastically reduced in the presence of increased amounts of nucleolin and corresponds to the level of reduction of 40 S pre-rRNA. Transcription from DNA templates containing various combinations of RNA polymerase I or II promoters in fusion with rDNA or CAT sequences was analyzed in the presence of elevated amounts of nucleolin. It was shown that nucleolin leads to transcription repression from a minimal polymerase I promoter, independently of the nature of the RNA sequence that is transcribed. Therefore, it is proposed that nucleolin affects RNA pol I transcription by acting directly on the transcription machinery or on the rDNA promoter sequences and not, as previously thought, through interaction with the nascent pre-rRNA (Roger, 2002).

Nucleolin, a multi-domain protein involved in ribosome biogenesis, has been shown to bind the consensus sequence (U/G)CCCG(A/G) in the context of a hairpin loop structure (nucleolin recognition element; NRE). Previous studies have shown that the first two RNA-binding domains in nucleolin (RBD12) are responsible for the interaction with the in vitro selected NRE (sNRE). The structures of nucleolin RBD12, sNRE and nucleolin RBD12-sNRE complex have been reported. A comparison of free and bound sNRE shows that the NRE loop becomes structured upon binding. From this observation, it is hypothesized that the disordered hairpin loop of sNRE facilitates conformational rearrangements when the protein binds. This study shows that nucleolin RBD12 is also sufficient for sequence-specific binding of two NRE sequences found in pre-rRNA, b1NRE and b2NRE. Structural investigations of the free NREs using NMR spectroscopy show that the b1NRE loop is conformationally heterogeneous, while the b2NRE loop is structured. The b2NRE forms a hairpin capped by a YNMG-like tetraloop. Comparison of the chemical shifts of sNRE and b2NRE in complex with nucleolin RBD12 suggests that the NRE consensus nucleotides adopt a similar conformation. These results show that a disordered NRE consensus sequence is not a prerequisite for nucleolin RBD12 binding (Finger, 2003).

Human replication protein A (RPA), the primary single-stranded DNA-binding protein, is inhibited after heat shock by complex formation with nucleolin. Nucleolin-RPA complex formation is stimulated after genotoxic stresses such as treatment with camptothecin or exposure to ionizing radiation. Complex formation in vitro and in vivo requires a 63-residue glycine-arginine-rich (GAR) domain located at the extreme C terminus of nucleolin, with this domain sufficient to inhibit DNA replication in vitro. Fluorescence resonance energy transfer studies demonstrate that the nucleolin-RPA interaction after stress occurs both in the nucleoplasm and in the nucleolus. Expression of the GAR domain or a nucleolin mutant (TM) with a constitutive interaction with RPA is sufficient to inhibit entry into S phase. Increasing cellular RPA levels by overexpression of the RPA2 subunit minimizes the inhibitory effects of nucleolin GAR or TM expression on chromosomal DNA replication. The arrest is independent of p53 activation by ATM or ATR and does not involve heightened expression of p21. These data reveal a novel cellular mechanism that represses genomic replication in response to genotoxic stress by inhibition of an essential DNA replication factor (Kim, 2005).

Remodeling machines play an essential role in the control of gene expression, but how their activity is regulated is not known. The nuclear protein nucleolin possesses a histone chaperone activity and this factor greatly enhances the activity of the chromatin remodeling machineries SWI/SNF and ACF. Interestingly, nucleolin is able to induce the remodeling by SWI/SNF of macroH2A, but not of H2ABbd nucleosomes, which are otherwise resistant to remodeling. This new histone chaperone promotes the destabilization of the histone octamer, helping the dissociation of a H2A-H2B dimer, and stimulates the SWI/SNF-mediated transfer of H2A-H2B dimers. Furthermore, nucleolin facilitates transcription through the nucleosome, which is reminiscent of the activity of the FACT complex. This work defines new functions for histone chaperones in chromatin remodeling and regulation of transcription and explains how nucleolin could act on transcription (Angelov, 2006).

Retinoblastoma protein (Rb) is a multifunctional tumor suppressor, frequently inactivated in certain types of human cancer. Nucleolin is an abundant multifunctional phosphoprotein of proliferating and cancerous cells, recently identified as cell cycle-regulated transcription activator, controlling expression of human papillomavirus type 18 (HPV18) oncogenes in cervical cancer. Here it was found that nucleolin is associated with Rb in intact cells in the G1 phase of the cell cycle, and the complex formation is mediated by the growth-inhibitory domain of Rb. Association with Rb inhibits the DNA binding function of nucleolin and in consequence the interaction of nucleolin with the HPV18 enhancer, resulting in Rb-mediated repression of the HPV18 oncogenes. The intracellular distribution of nucleolin in epithelial cells is Rb-dependent, and an altered nucleolin localization in human cancerous tissues results from a loss of Rb. These findings suggest that deregulated nucleolin activity due to a loss of Rb contributes to tumor development in malignant diseases, thus providing further insights into the molecular network for the Rb-mediated tumor suppression (Grinstein, 2006).

Eukaryotic genomes are packaged with histones and accessory proteins in the form of chromatin. RNA polymerases and their accessory proteins are sufficient for transcription of naked DNA, but not of chromatin, templates in vitro. In this study, nucleolin was purified and identified as a protein that allows RNA polymerase II to transcribe nucleosomal templates in vitro. Since immunofluorescence confirmed that nucleolin localizes primarily to nucleoli with RNA polymerase I, it was demonstrated that nucleolin allows RNA polymerase I transcription of chromatin templates in vitro. The results of chromatin immunoprecipitation experiments established that nucleolin is associated with chromatin containing rRNA genes transcribed by RNA polymerase I but not with genes transcribed by RNA polymerase II or III. Knockdown of nucleolin by RNA interference resulted in specific inhibition of RNA polymerase I transcription. It is therefore proposed that an important function of nucleolin is to permit RNA polymerase I to transcribe nucleolar chromatin (Richards, 2007).

Derepression of Y-linked multicopy protamine-like genes interferes with sperm nuclear compaction in D. melanogaster

Across species, sperm maturation involves the dramatic reconfiguration of chromatin into highly compact nuclei that enhance hydrodynamic ability and ensure paternal genomic integrity. This process is mediated by the replacement of histones by sperm nuclear basic proteins, also referred to as protamines. In humans, a carefully balanced dosage between two known protamine genes is required for optimal fertility. However, it remains unknown how their proper balance is regulated and how defects in balance may lead to compromised fertility. This study shows that a nucleolar protein, modulo, a homolog of nucleolin, mediates the histone-to-protamine transition during Drosophila spermatogenesis. modulo mutants display nuclear compaction defects during late spermatogenesis due to decreased expression of autosomal protamine genes (including Mst77F) and derepression of Y-linked multicopy Mst77F homologs, leading to the mutant's known sterility. Overexpression of Mst77Y in a wild-type background is sufficient to cause nuclear compaction defects, similar to modulo mutant, indicating that Mst77Y is a dominant-negative variant interfering with the process of histone-to-protamine transition. Interestingly, ectopic overexpression of Mst77Y caused decompaction of X-bearing spermatids nuclei more frequently than Y-bearing spermatid nuclei, although this did not greatly affect the sex ratio of offspring. It was further shown that modulo regulates these protamine genes at the step of transcript polyadenylation. It is concluded that the regulation of protamines mediated by modulo, ensuring the expression of functional ones while repressing dominant-negative ones, is critical for male fertility (Park, 2023).

The present study reveals a regulatory mechanism mediated by a nucleolar protein Modulo that balances the expression of protamine subtypes in D. melanogaster. This finding may represent a similar theme to what is seen in the fragile balance of PRM1 and PRM2 in mammalian fertility. In the case of Mst77Y, Y-linked multicopy Mst77F homologs, this study suggests that they have the ability to act as dominant-negative protamines and thus must be carefully regulated/repressed. The present study also confirmed that Mst77Y genes are expressed as proteins as suggested previously by the finding that several of the copies contain complete open-reading frames and is also consistent with small RNA sequencing revealing that the Mst77Y locus is not a source of small RNAs (Park, 2023).

Overexpression of Mst77Y dominantly interferes with Mst77F incorporation, leading to decompaction of sperm nuclei and their demise. Mst77Y genes feature differences from their autosomal homolog that further support the idea that they are dominant-negative versions of Mst77F and interfere with sperm chromatin compaction. Mst77Y-12, which retains the full ORF of Mst77F, exhibits 87% overall sequence homology to autosomal Mst77F. At the domain/motif level, the MST-HMG-box domain, suggested to be important for DNA binding, maintains 100% homology, while the coiled-coil motif and C-terminal domain maintain only ~79.5% and ~85% homology, respectively. It has been shown that the N-terminal domain of Mst77F, which contains the coiled-coil motif, interacts with the C-terminal domain to induce multimerization to mediate DNA compaction. The changes to Mst77Y at important regions may thus influence the multimerization of protamines and the formation of proper sperm chromatin structure, by interfering with the ability of the canonical version to multimerize. The notion that Mst77Y behaves as a dominant-negative version of Mst77F is further supported by the fact that overexpression of Mst77Y-3, a truncated version which does not contain the C-terminal domain, is still sufficient to cause defects in nuclear compaction (Park, 2023).

What is the potential 'function' of dominant-negative protamines? A few nonmutually exclusive possibilities are proposed. First, dominant-negative protamines may participate in meiotic drive, as suggested by recent works in D. simulans as well as D. melanogaster. Indeed, the data suggest that Mst77Y has the ability to disproportionally affect X-bearing spermatids. While this did not result in a large sex ratio distortion in offspring, this ability to harm a subset of developing spermatids during postmeiotic development may indicate the possibility that these protamine variants could be exploited by a meiotic drive system to unleash its own selfish purpose. Intriguingly, studies on the Winters sex-ratio meiotic drive system in D. simulans revealed that the driver, Dox, contains a large portion of the Protamine gene. While it has not been confirmed whether this protamine-like region is essential for sex ratio distortion, the derepression of Dox does seem to cause nuclear defects during spermiogenesis. It is proposed that a drive system that would be able to localize a dominant-negative protamine such as Mst77Y to a subset of spermatids containing one homolog over another could be quite successful at achieving bias. Alternatively, the dominant-negative version of a protamine may be utilized when spermatogenesis needs to be aborted (similar to the concept of 'programmed cell death'), for example under stress conditions. In such a case, dominant-negative protamines (such as Mst77Y) can be up-regulated to lead to abortive spermatogenesis. In such a scenario, a dominant-negative protamine may have a beneficial function for the organism. Yet another possibility that may contribute toward the rapid divergence of protamines is that protamine genes evolve to optimally package the genome, which may be greatly influenced by the composition of the most abundant sequences in a given genome, i.e., repetitive DNA such as satellite DNA. As these repetitive sequences are known to rapidly diverge across species, protamine genes may have to adapt to accommodate diverged repetitive DNA sequences, leading to rapid divergence and/or emergence of multiple protamine genes to optimally package different repetitive DNA with distinct structure/sequence. In such a scenario, fine-tuning the expression of different protamine genes may be critical. Additionally, if any protamine genes have evolved to optimally package certain satellite DNA, conversion of such protamine into a dominant-negative version can immediately target the chromosome that harbors the given satellite DNA, leading to meiotic drive that selectively harms the specific chromosome. This possibility is intriguing as the Segregation Distorter (SD) meiotic drive system in D. melanogaster is known to target Responder satellite DNA repeats and exhibits sperm nuclei decompaction similar to what is observed in this study. The possibility that dominant-negative protamines are involved in the decompaction of spermatid nuclei in the SD drive system remains to be studied (Park, 2023).

Taken together, this study identified a mechanism by which various protamine variants are coordinately regulated at the posttranscriptional level, possibly to achieve balanced expression of multiple protamine variants. A similar mechanism may be at play to fine-tune the expression levels of protamine variants in human and mouse, disruption of which is associated with compromised fertility (Park, 2023).


modulo: Regulation | Developmental Biology | Effects of Mutation | References

date revised: 5 August 2023

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