Chromatin assembly factor 1 subunit
p55 is observed mainly in the nuclei of syncytial blastoderm embryos (nuclear cycle 13) in both S or M phases. After cellularization, p55 appears to be nuclear except during M phase, in which it is present throughout the cell, possibly as a consequence of the partial breakdown of the nuclear envelope during mitosis. The level of p55 is highest during early embryogenesis and then decreases by a factor of approximately 10 in larvae, pupae, and adults. The amount of protein present in early embryos corresponds to about 220,000 molecules per nucleus, based on an estimated average of 12,000 nuclei per embryo. Thus p55 is a relatively abundant protein (Tyler, 1996).
Many proteins have been proposed to be involved in retinoblastoma protein (pRB)-mediated repression, but it is largely uncertain which cofactors are essential for pRB to repress endogenous E2F-regulated promoters. Advantage was taken of the stream-lined Drosophila dE2F/RBF pathway, which has only two E2Fs (dE2F1 and dE2F2), and two pRB family members (RBF1 and RBF2). With RNA interference (RNAi), potential corepressors were depleted and the elevated expression of groups of E2F target genes that are known to be directly regulated by RBF1 and RBF2 was sought. Previous studies have implicated histone deacetylase (HDAC) and SWI/SNF chromatin-modifying complexes in pRB-mediated repression. However, the results fail to support the idea that the SWI/SNF proteins are required for RBF-mediated repression and suggest that a requirement for HDAC activities is likely to be limited to a subset of targets. The chromatin assembly factor p55/dCAF-1 is essential for the repression of dE2F2-regulated targets. The removal of p55 deregulates the expression of E2F targets that are normally repressed by dE2F2/RBF1 and dE2F2/RBF2 complexes in a cell cycle-independent manner but has no effect on the expression of E2F targets that are normally coupled with cell proliferation. The results indicate that the mechanisms of RBF regulation at these two types of E2F targets are different and suggest that p55, and perhaps p55's mammalian orthologs RbAp46 and RbAp48, have a conserved function in repression by pRB-related proteins (Taylor-Harding, 2004).
Dendrite arborization patterns are critical determinants of neuronal function. To explore the basis of transcriptional regulation in dendrite pattern formation, RNA interference (RNAi) was used to screen 730 transcriptional regulators and 78 genes involved in patterning the stereotyped dendritic arbors of class I da neurons were identified in Drosophila. Most of these transcriptional regulators affect dendrite morphology without altering the number of class I dendrite arborization (da) neurons and fall primarily into three groups. Group A genes control both primary dendrite extension and lateral branching, hence the overall dendritic field. Nineteen genes within group A act to increase arborization, whereas 20 other genes restrict dendritic coverage. Group B genes appear to balance dendritic outgrowth and branching. Nineteen group B genes function to promote branching rather than outgrowth, and two others have the opposite effects. Finally, 10 group C genes are critical for the routing of the dendritic arbors of individual class I da neurons. Thus, multiple genetic programs operate to calibrate dendritic coverage, to coordinate the elaboration of primary versus secondary branches, and to lay out these dendritic branches in the proper orientation (Parrish, 2006; Full text of article).
To assay for the stereotyped dendrite arborization pattern of class I da neurons (hereafter referred to as class I neurons) in RNAi-based analysis of dendrite development, a Gal4 enhancer trap line (Gal4221) was used that is highly expressed in class I neurons and weakly expressed in class IV neurons during embryogenesis. Because of the simple and stereotyped dendritic arborization patterns of the dorsally located ddaD and ddaE, the studies of dendrite development focused on these two dorsally located class I neurons (Parrish, 2006).
To establish that RNAi is an efficient method to systematically study dendrite development in the Drosophila embryonic PNS, it was demonstrated that injecting embryos with double-stranded RNA (dsRNA) for green fluorescent protein (gfp) is sufficient to attenuate Gal-4221-driven expression of an mCD8::GFP fusion protein as measured by confocal microscopy. Next whether RNAi could efficiently phenocopy loss-of-function mutants known to affect dendrite development was tested. Similar to the mutant phenotype of short stop (shot), which encodes an actin/microtubule cross-linking protein, shot(RNAi) caused routing defects, dorsal overextension, and a reduction in lateral branching of dorsally extended primary dendrites. Likewise, RNAi of sequoia or flamingo resulted in overextension of ddaD and ddaE, RNAi of hamlet resulted in supernumerary class I neurons, and RNAi of tumbleweed resulted in supernumerary class I neurons and a range of arborization defects, consistent with the reported mutant phenotypes. Thus, RNAi is effective in generating reduction of function phenotypes in embryonic class I dendrites (Parrish, 2006).
RNAi of the Polycomb group (PcG) genes Su(z)12, E(z), esc, or Caf1 similarly caused an increase in branch number and an expansion of the receptive field of class I neurons. Consistent with the similar RNAi phenotypes for these genes, Su(z)12, E(z), esc, and Caf1 are components of the multiprotein esc/E(z) polycomb repressor complex. One critical role for PcG-mediated gene silencing is the regulation of hox gene expression. Therefore, Polycomb-mediated regulation of hox gene expression likely contributes to arborization of class I neurons (Parrish, 2006).
The p55 family WD40 repeat-containing histone chaperone proteins are components of several chromatin regulatory complexes (such as PRC2, NURF and CAF-1) and interact with histone H4, yet their functional relevance in vivo is unclear. This study used Drosophila as a genetic model to dissect the function of p55/Caf1 during development. In agree with a recent report, this study found that p55 is essential for Drosophila development and is required for cell proliferation and viability. However, the data further demonstrate that histone H3K27 di-/tri-methylation and PRC2-mediated gene silencing still occur normally when p55 is missing. p55 is also implicated in bridging chromatin regulatory complexes to the chromatin by binding to histone H4, but it was found that a transgene of p55 whose binding pocket is disrupted could still functionally substitute the wild-type p55 for survival. These studies suggest that p55 is not crucial for PRC2-mediated gene silencing in vivo, and the vital function of p55 is probably not dependent on its interaction with histone H4 (Wen, 2012).
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Chromatin assembly factor 1 subunit:
Biological Overview
| Evolutionary Homologs
| Regulation
| Developmental Biology
| Effects of RNAi
date revised: 10 August 2013
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