Essential role of
            <i>Drosophila Hdac1</i>
            in homeotic gene silencing

Chang, Yuh-Long; Peng, Yu-Huei; Pan, I-Ching; Sun, Der-Shan; King, Balas O.; Huang, Der-Hwa

doi:10.1073/pnas.171325498

Cited by 56 publications

(52 citation statements)

References 52 publications

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“…Genes with well-documented roles in modulating longevity are not among these direct targets (e.g., Sir2, Rpd3, foxo, InR, and others). However the histone deacetylases SIR2 and RPD3, which have been reported to modulate longevity in Drosophila, are also required for robust Polycomb silencing and associate with several larger PRC2 complexes (39)(40)(41)(42). For this reason, we examined their protein levels after stringent RNAi knockdown of E(Z) in S2 cells and found them to be unchanged (Fig.…”

Section: Resultsmentioning

confidence: 99%

Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance

Siebold¹,

Banerjee²,

Tie³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

177

149

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Polycomb Group (PcG) and Trithorax Group (TrxG) proteins are key epigenetic regulators of global transcription programs. Their antagonistic chromatin-modifying activities modulate the expression of many genes and affect many biological processes. Here we report that heterozygous mutations in two core subunits of Polycomb Repressive Complex 2 (PRC2), the histone H3 lysine 27 (H3K27)-specific methyltransferase E(Z) and its partner, the H3 binding protein ESC, increase longevity and reduce adult levels of trimethylated H3K27 (H3K27me3). Mutations in trithorax (trx), a well known antagonist of Polycomb silencing, elevate the H3K27me3 level of E(z) mutants and suppress their increased longevity. Like many long-lived mutants, E(z) and esc mutants exhibit increased resistance to oxidative stress and starvation, and these phenotypes are also suppressed by trx mutations. This suppression strongly suggests that both the longevity and stress resistance phenotypes of PRC2 mutants are specifically due to their reduced levels of H3K27me3 and the consequent perturbation of Polycomb silencing. Consistent with this, long-lived E(z) mutants exhibit derepression of Abd-B, a well-characterized direct target of Polycomb silencing, and Odc1, a putative direct target implicated in stress resistance. These findings establish a role for PRC2 and TRX in the modulation of organismal longevity and stress resistance and indicate that moderate perturbation of Polycomb silencing can increase longevity.aging | epigenetics | histone methyltransferase | Polycomb silencing

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Section: Resultsmentioning

confidence: 99%

Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance

Siebold¹,

Banerjee²,

Tie³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

177

149

View full text Add to dashboard Cite

show abstract

“…To identify the histone deacetylase(s) responsible for deacetylation of H3K27ac, we used RNAi to knock down two candidates, SIR2 and RPD3, both of which are associated with some PcG protein complexes and are required for robust Polycomb silencing (Chang et al, 2001;Furuyama et al, 2004;Tie et al, 2003;van der Vlag and Otte, 1999). Knockdown of RPD3, but not SIR2, elevated the H3K27ac level (Fig.…”

Section: Rpd3 Is Involved In the Deacetylation Of H3k27acmentioning

confidence: 99%

“…Both PRC2 and PRC1 associate, perhaps transiently, with the histone deacetylase RPD3, which is also required for Polycomb silencing (Chang et al, 2001;Tie et al, 2001;van der Vlag and Otte, 1999).…”

Section: Introductionmentioning

confidence: 99%

CBP-mediated acetylation of histone H3 lysine 27 antagonizesDrosophilaPolycomb silencing

et al. 2009

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Trimethylation of histone H3 lysine 27 (H3K27me3) by Polycomb repressive complex 2 (PRC2) is essential for transcriptional silencing of Polycomb target genes, whereas acetylation of H3K27 (H3K27ac) has recently been shown to be associated with many active mammalian genes. The Trithorax protein (TRX),which associates with the histone acetyltransferase CBP, is required for maintenance of transcriptionally active states and antagonizes Polycomb silencing, although the mechanism underlying this antagonism is unknown. Here we show that H3K27 is specifically acetylated by Drosophila CBP and its deacetylation involves RPD3. H3K27ac is present at high levels in early embryos and declines after 4 hours as H3K27me3 increases. Knockdown of E(Z)decreases H3K27me3 and increases H3K27ac in bulk histones and at the promoter of the repressed Polycomb target gene abd-A, suggesting that these indeed constitute alternative modifications at some H3K27 sites. Moderate overexpression of CBP in vivo causes a global increase in H3K27ac and a decrease in H3K27me3, and strongly enhances Polycomb mutant phenotypes. We also show that TRX is required for H3K27 acetylation. TRX overexpression also causes an increase in H3K27ac and a concomitant decrease in H3K27me3 and leads to defects in Polycomb silencing. Chromatin immunoprecipitation coupled with DNA microarray (ChIP-chip) analysis reveals that H3K27ac and H3K27me3 are mutually exclusive and that H3K27ac and H3K4me3 signals coincide at most sites. We propose that TRX-dependent acetylation of H3K27 by CBP prevents H3K27me3 at Polycomb target genes and constitutes a key part of the molecular mechanism by which TRX antagonizes or prevents Polycomb silencing.

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“…It is not only found in complex with several PcG proteins but there is also a significant overlap in chromosomal localisation on polytene chromosomes (Chang et al, 2001;Tie et al, 2001;Tie et al, 2003). However, it is noteworthy that this overlap is not complete and numerous PcG target genes are obviously not dependent on HDAC activity.…”

Section: Hdac1 In the Development Of Drosophila Melanogaster And Polymentioning

confidence: 99%

Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation

Brunmeir¹,

Lagger²,

Seiser³

2009

Int. J. Dev. Biol.

154

147

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During development from the fertilized egg to a multicellular organism, cell fate decisions have to be taken and cell lineage or tissue-specific gene expression patterns are created and maintained. These alterations in gene expression occur in the context of chromatin structure and are controlled by chromatin modifying enzymes. Gene disruption studies in different genetic systems have shown an essential role of various histone deacetylases (HDACs) during early development and cellular differentiation. In this review, we focus on the functions of the class I enzymes HDAC1 and HDAC2 during development in different organisms and summarise the current knowledge about their involvement in neurogenesis, myogenesis, haematopoiesis and epithelial cell differentiation. KEY WORDS: HDAC1, HDAC2, chromatin, differentiation, development Histone deacetylasesPosttranslational modifications of histones cause changes in the accessibility of DNA, thereby regulating many important cellular processes including transcription. Acetylation of core histones leads to a change in the net positive charge of histone tails and local opening of chromatin structure, a feature of transcriptionally active genes. On the other hand, deacetylated histone tails interact more closely with DNA and lead to a repressive state. Histone deacetylases (HDACs) catalyse the removal of acetyl groups from histone tails and are therefore considered as transcriptional corepressors. In addition to histones, HDACs also deacetylate non-histone proteins, such as the cytoskeletal protein tubulin (Hubbert et al., 2002) or transcription factors including p53 (Luo et al., 2000), E2F1 (MartinezBalbas et al., 2000) and YY1 (Yao et al., 2001). In fact, phylogenetic analysis suggests that the enzymatic activity was initially directed against non-histone proteins in a common ancestor devoid of histones (Gregoretti et al., 2004). In mammals, 18 deacetylases have been identified so far. These enzymes have been divided into 4 classes based on sequence similarity: Classic HDACs comprise class I (Saccharomyces cerevisiae Rpd3-like), class II (Saccharomyces cerevisiae Hda1-like) and class IV (HDAC11-like) enzymes. Class III consists of NAD-dependent, functionally unrelated Sir2-like deacetylases Int. J. Dev. Biol. 53: 275-289 (2009) Abbreviations used in this paper: HAT, histone acetyltransferase; HDA, HDAC, histone deacetylase; HDI, HDAC inhibitor; NuRD, nucleosome remodelling and deacetylase complex; Rpd3, reduced potassium dependency 3.named "sirtuins". Class I, II and IV HDACs are members of an ancient enzyme family, highly conserved throughout eukaryotic and prokaryotic evolution and are found in animals, plants, fungi, archaebacteria and eubacteria (Gregoretti et al., 2004). Class I histone deacetylasesPhylogenetic analysis revealed that class I genes in animals can be grouped into HDAC1/HDAC2, HDAC3 and HDAC8-like genes. Members of each subclass have been identified in protostomia (Oger et al., 2008) and deuterostomia. Species analysed so far carry orthologs (...

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Essential role of Drosophila Hdac1 in homeotic gene silencing

Cited by 56 publications

References 52 publications

Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance

Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance

CBP-mediated acetylation of histone H3 lysine 27 antagonizesDrosophilaPolycomb silencing

Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation

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