Bivalent complexes of PRC1 with orthologs of BRD4 and MOZ/MORF target developmental genes in <i>Drosophila</i>

Kang, Heather A.; Jung, Youngsook L.; McElroy, Kyle A.; Zee, Barry M.; Wallace, Heather A.; Woolnough, Jessica L.; Park, Peter J.; Kuroda, Mitzi I.

doi:10.1101/gad.305987.117

Cited by 27 publications

(48 citation statements)

References 67 publications

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“…We next examined the binding of the recruiters and PcG proteins with respect to H3K27me3 domains. Consistent with recent studies (26)(27)(28), the binding of PcG proteins is not restricted to H3K27me3 domains. In fact, for most analyzed PcG proteins except Pc, more than 80% of peaks are outside of H3K27me3 domains (SI Appendix, Fig.…”

Section: Resultssupporting

confidence: 91%

Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho

Brown

Sun

Kassis

2018

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

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Polycomb group (PcG) proteins maintain the silenced state of key developmental genes in animals, but how these proteins are recruited to specific regions of the genome is still poorly understood. In , PcG proteins are recruited to Polycomb response elements (PREs) that include combinations of sites for sequence specific DNA binding "PcG recruiters," including Pho, Cg, and Spps. To understand their roles in PcG recruitment, we compared Pho-, Cg-, and Spps-binding sites against H3K27me3 and key PcG proteins by ChIP-seq in wild-type and mutant third instar larvae. H3K27me3 in canonical Polycomb domains is decreased after the reduction of any recruiter. Reduction of Spps and Pho, but not Cg, causes the redistribution of H3K27me3 to heterochromatin. Regions with dramatically depleted H3K27me3 after Spps knockout are usually accompanied by decreased Pho binding, suggesting their cooperative binding. PcG recruiters, the PRC2 component E(z), and the PRC1 components Psc and Ph cobind thousands of active genes outside of H3K27me3 domains. This study demonstrates the importance of distinct PcG recruiters for the establishment of unique Polycomb domains. Different PcG recruiters can act both cooperatively and independently at specific PcG target genes, highlighting the complexity and diversity of PcG recruitment mechanisms.

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Section: Resultssupporting

confidence: 91%

Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho

Brown

Sun

Kassis

2018

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

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“…Similar to our results, Zheng et al reported that H3K4me3 modified by menin‐MLL complex (one component of TrxG complex) at the P3 and P4 promoters contributes to the robust expression of IGF2 in Hep3B cells . Another report by Kang et al showed that the choice between a transcriptionally active or silent state was associated with the enrichment of increased TrxG or PRC2 proteins at poised bivalent genes, respectively, and a decrease in TrxG impelled genes to resolve into a transition toward silencing . Taken together, these findings suggest that the expression of IGF2 is regulated by the bivalent modifications of H3K4me3 and H3K27me3 in HCC, and 91H directly binds to TrxG complex, and recruits it to the targeted P3 and P4 promoters of IGF2 gene, which further results in increased enrichment of H3K4me3 and decreased enrichment of H3K27me3 (owing to the possibility of competitive PRC2 recruitment reduction).…”

Section: Discussionsupporting

confidence: 92%

Long noncoding RNA 91H overexpression contributes to the growth and metastasis of HCC by epigenetically positively regulating IGF2 expression

Wang

Shi

et al. 2019

Liver International

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are contributed equally to this work.Abbreviations: ChIP, Chromatin immunoprecipitation; H3K27me3, H3 lysine 27 trimethylation; H3K4me3, H3 lysine 4 trimethylation; HCC, Hepatocellular carcinoma; IGF2, Insulin-like growth factor 2; lncRNAs, Long noncoding RNAs; MANT, the matched adjacent nontumourous tissues; MTT, the methyl thiazolyl tetrazolium; NALT, the normal adult liver tissues;Neg-ctrl, negative control cells; PI, propidium iodide; PRC2, polycomb repressive complex 2; RIP, the RNA immunoprecipitation; sh91H, 91H shRNA; si91H, 91H siRNA; siRBBP5, RBBP5 siRNA; TEPV, tumour embolus of portal vein; TrxG, Trithorax group. AbstractBackground & Aims: Long noncoding RNA 91H is transcribed from the H19/IGF2 locus and contributes to the development of breast and oesophagus cancers by regulating the expression of IGF2, but the regulation mechanism remains poorly characterized. Here, we explored the role of 91H in hepatocellular carcinoma (HCC) and the mechanism of IGF2 expression regulation by 91H.Methods: Firstly, the expression of 91H was analysed in HCC by quantitative RT-PCR, the association of 91H with survival was evaluated by the Kaplan-Meier method and the effect of 91H on the growth and invasion of HCC was investigated by the in vitro and in vivo studies. Then, the association of 91H with the expression of IGF2 was evaluated in HCC tissues, and the effect of 91H on the expression of IGF2 was investigated by 91H knockdown. Finally, the binding of RBBP5 to 91H and the binding of RBBP5, activating H3K4me3 mark and repressive H3K27me3 mark to the P3 and P4 promoters of IGF2 gene were studied by RIP and ChIP respectively. Results:The overexpression of 91H was found in HCC and in association with the growth, metastasis and shorter survival time of HCC. The knockdown of 91H downregulated the IGF2 expression in HCC, and the mechanism was correlated with the decreased enrichment of RBBP5 and H3K4me3 and increased enrichment of H3K27me3 at the bivalent P3 and P4 promoters. Conclusions:The overexpression of 91H promotes tumour growth and metastasis, and is associated with a poor prognosis of HCC at least partially by positively regulating the expression of IGF2 through bivalent histone modification changes characterized by H3K4me3 and H3K27me3 at the P3 and P4 promoters. K E Y W O R D S 91H, bivalent histone modifications, hepatocellular carcinoma, IGF2, Long noncoding RNA | 457 YI et al.

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“…ChIP-seq identified two groups of PRC1/Br140 genomic binding sites that were either defined by strong H3K27me3 signal or strong H3K27ac signal (i.e., actively transcribed genes). Both groups were also marked with narrow peaks of H3K4me3 at the TSS (Kang et al 2017). These recent findings also argue for the existence of bivalent-like promoters outside of vertebrates, at least with respect to the binding of chromatin regulatory complexes, and extends the model to suggest that acetylation may be important in the resolution of bivalent protein complexes during development.…”

Section: Discussionsupporting

confidence: 63%

Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells

et al. 2018

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Planarian flatworms have an indefinite capacity to regenerate missing or damaged body parts owing to a population of pluripotent adult stems cells called neoblasts (NBs). Currently, little is known about the importance of the epigenetic status of NBs and how histone modifications regulate homeostasis and cellular differentiation. We have developed an improved and optimized ChIP-seq protocol for NBs in and have generated genome-wide profiles for the active marks H3K4me3 and H3K36me3, and suppressive marks H3K4me1 and H3K27me3. The genome-wide profiles of these marks were found to correlate well with NB gene expression profiles. We found that genes with little transcriptional activity in the NB compartment but which switch on in post-mitotic progeny during differentiation are bivalent, being marked by both H3K4me3 and H3K27me3 at promoter regions. In further support of this hypothesis, bivalent genes also have a high level of paused RNA Polymerase II at the promoter-proximal region. Overall, this study confirms that epigenetic control is important for the maintenance of a NB transcriptional program and makes a case for bivalent promoters as a conserved feature of animal stem cells and not a vertebrate-specific innovation. By establishing a robust ChIP-seq protocol and analysis methodology, we further promote planarians as a promising model system to investigate histone modification-mediated regulation of stem cell function and differentiation.

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Bivalent complexes of PRC1 with orthologs of BRD4 and MOZ/MORF target developmental genes in Drosophila

Cited by 27 publications

References 67 publications

Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho

Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho

Long noncoding RNA 91H overexpression contributes to the growth and metastasis of HCC by epigenetically positively regulating IGF2 expression

Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells

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