KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

CpG islands (CGIs) are associated with most mammalian gene promoters. A subset of CGIs act as polycomb response elements (PREs) and are recognized by the polycomb silencing systems to regulate expression of genes involved in early development. How CGIs function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that KDM2B (FBXL10) specifically recognizes non-methylated DNA in CGIs and recruits the polycomb repressive complex 1 (PRC1). This contributes to histone H2A lysine 119 ubiquitylation (H2AK119ub1) and gene repression. Unexpectedly, we also find that CGIs are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CGI-associated genes for susceptibility to polycomb-mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CGIs by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CGIs as mammalian PREs.

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Identification of polycomb repressive complex 1 and 2 core components in hexaploid bread wheat

BMC Plant Biology ◽

10.1186/s12870-020-02384-6 ◽

2020 ◽

Vol 20 (S1) ◽

Author(s):

Beáta Strejčková ◽

Radim Čegan ◽

Ales Pecinka ◽

Zbyněk Milec ◽

Jan Šafář

Keyword(s):

Bread Wheat ◽

Developmental Stages ◽

Gene Families ◽

Polycomb Group ◽

Transcriptional Analysis ◽

Histone H2a ◽

Polycomb Repressive Complex ◽

Core Components ◽

High Level ◽

Polycomb Repressive Complex 1

Abstract Background Polycomb repressive complexes 1 and 2 play important roles in epigenetic gene regulation by posttranslationally modifying specific histone residues. Polycomb repressive complex 2 is responsible for the trimethylation of lysine 27 on histone H3; Polycomb repressive complex 1 catalyzes the monoubiquitination of histone H2A at lysine 119. Both complexes have been thoroughly studied in Arabidopsis, but the evolution of polycomb group gene families in monocots, particularly those with complex allopolyploid origins, is unknown. Results Here, we present the in silico identification of the Polycomb repressive complex 1 and 2 (PRC2, PRC1) subunits in allohexaploid bread wheat, the reconstruction of their evolutionary history and a transcriptional analysis over a series of 33 developmental stages. We identified four main subunits of PRC2 [E(z), Su(z), FIE and MSI] and three main subunits of PRC1 (Pc, Psc and Sce) and determined their chromosomal locations. We found that most of the genes coding for subunit proteins are present as paralogs in bread wheat. Using bread wheat RNA-seq data from different tissues and developmental stages throughout plant ontogenesis revealed variable transcriptional activity for individual paralogs. Phylogenetic analysis showed a high level of protein conservation among temperate cereals. Conclusions The identification and chromosomal location of the Polycomb repressive complex 1 and 2 core components in bread wheat may enable a deeper understanding of developmental processes, including vernalization, in commonly grown winter wheat.

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Decision letter: KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

10.7554/elife.00205.019 ◽

2012 ◽

Keyword(s):

Cpg Islands ◽

Polycomb Repressive Complex ◽

Polycomb Repressive Complex 1

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Identification of Polycomb Repressive Complex 1 and 2 Core Components in Hexaploid Bread Wheat

10.1101/703546 ◽

2019 ◽

Author(s):

Beáta Strejčková ◽

Radim Čegan ◽

Ales Pecinka ◽

Zbyněk Milec ◽

Jan Šafář

Keyword(s):

Bread Wheat ◽

Developmental Stages ◽

Gene Families ◽

Polycomb Group ◽

Transcriptional Analysis ◽

Histone H2a ◽

Polycomb Repressive Complex ◽

Polycomb Repressive Complex 2 ◽

Core Components ◽

Polycomb Repressive Complex 1

ABSTRACTPolycomb repressive complex 1 and 2 play important roles in epigenetic gene regulation by posttranslationally modifying specific histone residues. Polycomb repressive complex 2 is responsible for the trimethylation of lysine 27 on histone H3, while Polycomb repressive complex 1 catalyzes the monoubiquitination of histone H2A at lysine 119. Although these biochemical functions are evolutionarily conserved, studies in animals and plants, mainly Arabidopsis thaliana, showed that specific subunits have evolved into small gene families, with individual members acting at different developmental stages or responding to specific environmental stimuli. However, the evolution of polycomb group gene families in monocots, particularly those with complex allopolyploid origins, is unknown. Here, we present the in silico identification of the Polycomb repressive complex 1 and 2 subunits in allohexaploid bread wheat, the reconstruction of their evolutionary history and a transcriptional analysis over a series of 33 developmental stages. The identification and chromosomal location of the Polycomb repressive complex 1 and 2 core components in bread wheat may enable a deeper understanding of developmental processes, including vernalization in commonly grown winter wheat.

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Author response: KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

10.7554/elife.00205.020 ◽

2012 ◽

Author(s):

Anca M Farcas ◽

Neil P Blackledge ◽

Ian Sudbery ◽

Hannah K Long ◽

Joanna F McGouran ◽

...

Keyword(s):

Cpg Islands ◽

Author Response ◽

Polycomb Repressive Complex ◽

Polycomb Repressive Complex 1

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Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation

Molecular Cell ◽

10.1016/j.molcel.2013.01.016 ◽

2013 ◽

Vol 49 (6) ◽

pp. 1134-1146 ◽

Cited By ~ 248

Author(s):

Xudong Wu ◽

Jens Vilstrup Johansen ◽

Kristian Helin

Keyword(s):

Cpg Islands ◽

Polycomb Repressive Complex ◽

Polycomb Repressive Complex 1

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Polycomb repressive complex 1 defines the nucleosome landscape but not accessibility at target genes

10.1101/280305 ◽

2018 ◽

Author(s):

Hamish W King ◽

Robert J Klose

Keyword(s):

Target Genes ◽

Nucleosome Occupancy ◽

Embryonic Stem ◽

Chromatin Accessibility ◽

Polycomb Group ◽

Gene Promoters ◽

Polycomb Repressive Complex ◽

Chromatin Domains ◽

Genetic Ablation ◽

Polycomb Repressive Complex 1

ABSTRACTPolycomb group (PcG) proteins are transcriptional repressors that play important roles regulating gene expression during animal development. In vitro experiments have shown that PcG protein complexes can compact chromatin limiting the activity of chromatin remodelling enzymes and access of the transcriptional machinery to DNA. In fitting with these ideas, gene promoters associated with PcG proteins have been reported to be less accessible than other gene promotors. However, it remains largely untested in vivo whether PcG proteins define chromatin accessibility or other chromatin features. To address this important question, we measured chromatin accessibility and examined the nucleosome landscape at PcG protein-bound promoters in mouse embryonic stem cells using the assay for transposase accessible chromatin (ATAC)-seq. Combined with genetic ablation strategies, we unexpectedly discover that although PcG protein-occupied gene promoters exhibit reduced accessibility, this does not rely on PcG proteins. Instead, the Polycomb repressive complex 1 (PRC1) appears to play a unique role in driving elevated nucleosome occupancy and decreased nucleosomal spacing in Polycomb chromatin domains. Our new genome-scale observations argue, in contrast to the prevailing view, that PcG proteins and Polycomb chromatin domains do not significantly affect chromatin accessibility and highlight an underappreciated complexity in the relationship between chromatin accessibility, the nucleosome landscape and PcG-mediated transcriptional repression.

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Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide

Molecular Cell ◽

10.1016/j.molcel.2014.06.005 ◽

2014 ◽

Vol 55 (3) ◽

pp. 347-360 ◽

Cited By ~ 262

Author(s):

Eva Madi Riising ◽

Itys Comet ◽

Benjamin Leblanc ◽

Xudong Wu ◽

Jens Vilstrup Johansen ◽

...

Keyword(s):

Gene Silencing ◽

Cpg Islands ◽

Polycomb Repressive Complex ◽

Polycomb Repressive Complex 2 ◽

Genome Wide

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Polycomb repressive complex 1 modifies transcription of active genes

Science Advances ◽

10.1126/sciadv.1700944 ◽

2017 ◽

Vol 3 (8) ◽

pp. e1700944 ◽

Cited By ~ 26

Author(s):

Michelle Pherson ◽

Ziva Misulovin ◽

Maria Gause ◽

Kathie Mihindukulasuriya ◽

Amanda Swain ◽

...

Keyword(s):

Polycomb Repressive Complex ◽

Polycomb Repressive Complex 1 ◽

Active Genes

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Landscape Of HOXA Genes Methylation in Colorectal Cancer

Progress In Microbes & Molecular Biology ◽

10.36877/pmmb.a0000085 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Muhiddin Ishak ◽

Rashidah Baharudin ◽

Loh Teng-Hern Tan ◽

Learn-Han Lee ◽

Nurul-Syakima Ab Mutalib

Keyword(s):

Colorectal Cancer ◽

Cancer Susceptibility ◽

Cpg Islands ◽

Methylation Pattern ◽

Gene Promoters ◽

Normal Tissues ◽

Genes Encoding ◽

Hoxa Genes ◽

A Minor ◽

Hoxa Gene

Colorectal cancer (CRC) is among the most common cancers worldwide and the second leading cause of cancer-related death in Malaysia. The HOXA gene cluster is a family of Homeobox A genes encoding transcriptional regulators that play vital roles in cancer susceptibility and progression. Dysregulated HOXA expression influences various aspects of carcinogenesis processes. Therefore, this study aims to elucidate the methylation landscape of HOXA genes in CRC. Twelve pairs of CRC — adjacent normal tissues were subjected to Infinium DNA MethyEPIC array. Differentially methylatedregions were identified using the ChAMP Bioconductor and methylation levels of HOXA genes were manually curated. We identified 100 significantly differentially methylated probes annotated to HOXA genes. HOXA3 has the highest number of differentially methylated probes (n=27), followed by HOXA2 (n=20) and HOXA4 (n=14). The majority (43%) of the probes were located at the transcription start site (TSS) 200, which is one of the gene promoters. In respect to CpG islands (CGI), the probes were equally located in the island and shore regions (47% each) while a minor percentage was in the shelf (6%). Our work gave a comprehensive assessment of the DNA methylation pattern of HOXA genes and provide the first evidence of HOXA2, HOXA3 and HOXA4 differential methylation in Malaysian CRC. The new knowledge from this study can be utilized to further increase our understanding of CRC methylomics, particularly on the homeobox A genes. The prognostic and diagnostic roles of the differentially methylated HOXA genes warrant future investigations.

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