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KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE126864 | GEO | 2019/07/03

REPOSITORIES: GEO

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KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity.

Project description:CpG islands (CGIs) are associated with the majority of mammalian gene promoters and function to recruit chromatin modifying enzymes. It has therefore been proposed that CGIs regulate gene expression through chromatin-based mechanisms, however in most cases this has not been directly tested. Here, we reveal that the histone H3 lysine 36 (H3K36) demethylase activity of the CGI-binding KDM2 proteins contributes only modestly to the H3K36me2-depleted state at CGI-associated gene promoters and is dispensable for normal gene expression. Instead, we discover that KDM2 proteins play a widespread and demethylase-independent role in constraining gene expression from CGI-associated gene promoters. We further show that KDM2 proteins shape RNA Polymerase II occupancy but not chromatin accessibility at CGI-associated promoters. Together this reveals a demethylase-independent role for KDM2 proteins in transcriptional repression and uncovers a new function for CGIs in constraining gene expression.

| S-EPMC6753492 | biostudies-literature

KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [ATAC-seq]

Project description:CpG islands (CGI) are associated with the majority of mammalian gene promoters and function to recruit chromatin modifying enzymes. It has therefore been proposed that CGIs regulate gene expression through chromatin-based mechanisms, however in most cases this has not been directly tested. Here, we reveal that the histone H3 lysine 36 (H3K36) demethylase activity of the CGI-binding KDM2 proteins contributes only modestly to the H3K36me2-depleted state at CGI-associated gene promoters and is dispensable for normal gene expression. Instead, we discover that KDM2 proteins play a widespread and demethylase-independent role in constraining gene expression from CGI-associated gene promoters. We further show that KDM2 proteins shape RNA Polymerase II occupancy but not chromatin accessibility at CGI-associated promoters. Together this reveals a demethylase-independent role for KDM2 proteins in transcriptional repression and uncovers a new function for CGIs in constraining gene expression.

2019-07-03 | GSE126863 | GEO

KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [ChIP-seq]

2019-07-03 | GSE126862 | GEO

KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [RNA-seq]

2019-07-03 | GSE126861 | GEO

KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity

Project description:KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity

| PRJNA523563 | ENA

KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [ATAC-seq]

Project description:KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [ATAC-seq]

| PRJNA523566 | ENA

KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [ChIP-seq]

Project description:KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [ChIP-seq]

| PRJNA523568 | ENA

KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [RNA-seq]

Project description:KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity [RNA-seq]

| PRJNA523567 | ENA

CpG-island promoters drive transcription of human telomeres.

Project description:The longstanding dogma that telomeres, the heterochromatic extremities of linear eukaryotic chromosomes, are transcriptionally silent was overturned by the discovery that DNA-dependent RNA polymerase II (RNAPII) transcribes telomeric DNA into telomeric repeat-containing RNA (TERRA). Here, we show that CpG dinucleotide-rich DNA islands, shared among multiple human chromosome ends, promote transcription of TERRA molecules. TERRA promoters sustain cellular expression of reporter genes, are located immediately upstream of TERRA transcription start sites, and are bound by active RNAPII in vivo. Finally, the identified promoter CpG dinucleotides are methylated in vivo, and cytosine methylation negatively regulates TERRA abundance. The existence of subtelomeric promoters, driving TERRA transcription from independent chromosome ends, supports the idea that TERRA exerts fundamental functions in the context of telomere biology.

| S-EPMC2779677 | biostudies-literature

Human genes with CpG island promoters have a distinct transcription-associated chromatin organization.

Project description:BackgroundMore than 50% of human genes initiate transcription from CpG dinucleotide-rich regions referred to as CpG islands. These genes show differences in their patterns of transcription initiation, and have been reported to have higher levels of some activation-associated chromatin modifications.ResultsHere we report that genes with CpG island promoters have a characteristic transcription-associated chromatin organization. This signature includes high levels of the transcription elongation-associated histone modifications H4K20me1, H2BK5me1 and H3K79me1/2/3 in the 5' end of the gene, depletion of the activation marks H2AK5ac, H3K14ac and H3K23ac immediately downstream of the transcription start site (TSS), and characteristic epigenetic asymmetries around the TSS. The chromosome organization factor CTCF may be bound upstream of RNA polymerase in most active CpG island promoters, and an unstable nucleosome at the TSS may be specifically marked by H4K20me3, the first example of such a modification. H3K36 monomethylation is only detected as enriched in the bodies of active genes that have CpG island promoters. Finally, as expression levels increase, peak modification levels of the histone methylations H3K9me1, H3K4me1, H3K4me2 and H3K27me1 shift further away from the TSS into the gene body.ConclusionsThese results suggest that active genes with CpG island promoters have a distinct step-like series of modified nucleosomes after the TSS. The identity, positioning, shape and relative ordering of transcription-associated histone modifications differ between genes with and without CpG island promoters. This supports a model where chromatin organization reflects not only transcription activity but also the type of promoter in which transcription initiates.

| S-EPMC3580500 | biostudies-literature

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