Cohesin and Polycomb Proteins Functionally Interact to Control Transcription at Silenced and Active Genes

Schaaf, Cheri A.; Misulovin, Ziva; Gause, Maria; Koenig, Amanda; Gohara, David W.; Watson, Audrey; Dorsett, Dale

doi:10.1371/journal.pgen.1003560

Cited by 104 publications

(189 citation statements)

References 53 publications

(123 reference statements)

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“…5B). Similar to the results from another study (43) ChIP-qPCR showed that no Psc was present at these sites (Fig. 5C).…”

Section: Resultssupporting

confidence: 90%

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Combgap contributes to recruitment of Polycomb group proteins in Drosophila

Ray

Mitra

et al. 2016

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

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Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG proteins are organized into multiprotein complexes that are recruited to DNA via cis-acting elements known as “Polycomb response elements” (PREs). In Drosophila, PREs consist of binding sites for many different DNA-binding proteins, some known and others unknown. Identification of these DNA-binding proteins is crucial to understanding the mechanism of PcG recruitment to PREs. We report here the identification of Combgap (Cg), a sequence-specific DNA-binding protein that is involved in recruitment of PcG proteins. Cg can bind directly to PREs via GTGT motifs and colocalizes with the PcG proteins Pleiohomeotic (Pho) and Polyhomeotic (Ph) at the majority of PREs in the genome. In addition, Cg colocalizes with Ph at a number of targets independent of Pho. Loss of Cg leads to decreased recruitment of Ph at only a subset of sites; some of these sites are binding sites for other Polycomb repressive complex 1 (PRC1) components, others are not. Our data suggest that Cg can recruit Ph in the absence of PRC1 and illustrate the diversity and redundancy of PcG protein recruitment mechanisms.

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“…5B). Similar to the results from another study (43) ChIP-qPCR showed that no Psc was present at these sites (Fig. 5C).…”

Section: Resultssupporting

confidence: 90%

“…Cg and Ph colocalize to many sites in the genome independent of Pho, and many of these sites are not in H3K27me3 domains. Similarly, Schaaf et al (43) found that a large number of Ph sites occur outside H3K27me3 domains. Our data suggest that Cg may play a role in recruiting Ph to these sites.…”

Section: Resultsmentioning

confidence: 81%

Combgap contributes to recruitment of Polycomb group proteins in Drosophila

Ray

Mitra

et al. 2016

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

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“…Consistent with this observation, the genome-wide binding pattern of PRC1 is highly correlated with inactive genes marked by H3K27me3. However, several recent studies have revealed that PRC1 is also bound at promoters of many active genes that contain little or no H3K27me3 (21,22), suggesting that PRC1 can be targeted independent of the PC chromodomain and may also negatively modulate transcription of active genes.…”

mentioning

confidence: 99%

Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain

Tie

Banerjee

et al. 2016

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

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Drosophila Polycomb (PC), a subunit of Polycomb repressive complex 1 (PRC1), is well known for its role in maintaining repression of the homeotic genes and many others and for its binding to trimethylated histone H3 on Lys 27 (H3K27me3) via its chromodomain. Here, we identify a novel activity of PC: inhibition of the histone acetylation activity of CREB-binding protein (CBP). We show that PC and its mammalian CBX orthologs interact directly with the histone acetyltransferase (HAT) domain of CBP, binding to the previously identified autoregulatory loop, whose autoacetylation greatly enhances HAT activity. We identify a conserved PC motif adjacent to the chromodomain required for CBP binding and show that PC binding inhibits acetylation of histone H3. CBP autoacetylation impairs PC binding in vitro, and PC is preferentially associated with unacetylated CBP in vivo. PC knockdown elevates the acetylated H3K27 (H3K27ac) level globally and at promoter regions of some genes that are bound by both PC and CBP. Conversely, PC overexpression decreases the H3K27ac level in vivo and also suppresses CBP-dependent Polycomb phenotypes caused by overexpression of Trithorax, an antagonist of Polycomb silencing. We find that PC is physically associated with the initiating form of RNA polymerase II (Pol II) and that many promoters co-occupied by PC and CBP are associated with paused Pol II, suggesting that PC may play a role in Pol II pausing. These results suggest that PC/PRC1 inhibition of CBP HAT activity plays a role in regulating transcription of both repressed and active PC-regulated genes.Polycomb | CBP | acetylation | histone H3K27 | Drosophila

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“…First we combined the ChIP-seq data for H4K20me1 generated in this study with the ChIP-chip data for Pc and ChIP-seq data for H3K27me3 reported previously [21,51]. A total of 1 051 genes were chosen for the subsequent analysis since they seem to be the targets of both PRC2 and PRC1, i.e., regulated by the hierarchically recruited PcG proteins ( Figure 4A, Pc + H3K27me3 + genes).…”

Section: H3k27me3 Pc and H4k20me1 Function Together To Positively Rementioning

confidence: 99%

“…However, several isolated studies in Drosophila and mammals suggest a positive regulatory role of PcGs in transcription [19][20][21], but the underlying mechanism is largely unknown. Most of these studies have focused on the positive role of PcGs during carcinogenesis [22][23][24][25][26], whereas such regulation during normal development has been poorly investigated [27][28][29].…”

Section: Introductionmentioning

confidence: 99%