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ZBTB2 as a novel reader for unmethylated DNA

ABSTRACT: In this study, we investigated the dynamics during differentiation of the in vivo binding sites of ZBTB2, a putative reader for unmethylated DNA. We performed DNA pull-downs followed by mass spectrometry, using a genomic sequence containing either unmethylated or methylated CpGs, to study the influence of DNA methylation on ZBTB2 binding. Additionally, we performed interaction proteomics to identify ZBTB2 interaction partners. We found that ZBTB2 recruits a zinc finger module of three proteins to unmethylated DNA.

OTHER RELATED OMICS DATASETS IN: PRJNA395559PRJNA395560PRJNA395548GSE101802

INSTRUMENT(S): Orbitrap Fusion, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Ino Karemaker

LAB HEAD: Michiel Vermeulen

PROVIDER: PXD007099 | Pride | 2018-01-29

REPOSITORIES: Pride

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ZBTB2 reads unmethylated CpG island promoters and regulates embryonic stem cell differentiation.

Karemaker Ino D ID Vermeulen Michiel M

EMBO reports 20180201 4

Proteins that bind to DNA depending on its methylation status play an important role in methylation-mediated regulation of gene expression. Using a variety of genomics and proteomics approaches, we identify zinc finger and BTB domain-containing protein 2 (ZBTB2) as a reader of unmethylated DNA in mouse embryonic stem cells. ZBTB2 preferentially binds to CpG island promoters, where it acts as a transcriptional activator. The binding of ZBTB2 to its targets is direct and independent of two other z ...[more]

PMID: 29437775

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ZBTB2 as a novel reader for unmethylated DNA

Project description:ZBTB2 as a novel reader for unmethylated DNA

| PRJNA395548 | ENA

ZBTB2 as a novel reader for unmethylated DNA [ChIP-seq]

Project description:DNA methylation is a dynamic epigenetic modification that plays a key role in various cellular processes. Proteins that bind to DNA depending on its methylation status are thought to play an important role in DNA methylation-mediated gene expression. Using a variety of genomics and proteomics approaches, we identified ZBTB2 as a novel reader of unmethylated DNA. ZBTB2, which forms a complex with ZBTB25 and ZNF639, preferentially binds at CpG island promoters in mouse embryonic stem cells, from where it regulates genes that are involved in the exit from pluripotency. Binding of ZBTB2 to target genes is mostly associated with gene activation. Furthermore, ZBTB2 is intricately interwoven with DNA methylation, as we found not only that its binding to DNA is methylation-sensitive, but also that ZBTB2 regulates the turnover of methylated DNA. Summarising, we propose that ZBTB2 is a DNA methylation-sensitive transcription factor that is involved in cellular differentiation.

2018-01-29 | GSE101800 | GEO

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The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands

Project description:CpG-islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 possesses an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. Absence of SAMD1 impairs ES cell differentiation processes, leading to mis-regulation of key biological pathways. Together, our work establishes SAMD1 as a novel chromatin regulator acting at unmethylated CGIs.

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NuRD-interacting protein ZFP296 regulates genome-wide NuRD localization and differentiation of mouse embryonic stem cells

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The histone acetyltransferase KAT6A is recruited to unmethylated CpG islands via a DNA-binding winged helix domainThe histone acetyltransferase KAT6A is recruited to unmethylated CpG islands via a DNA-binding winged helix domain

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MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain

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