Molecular mechanisms and potential functions of histone demethylases

Kooistra, Susanne M.; Helin, Kristian

doi:10.1038/nrm3327

Cited by 739 publications

(531 citation statements)

References 201 publications

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“…Histone methylation affects gene expression with distinct localized patterns. H3K4me3 in the promoter region increases transcription, whereas H3K9me3 in the gene body and H3K27me3 in both the promoter and gene body are associated with repression [10,11]. The fact that JmjC proteins need O 2 for their catalytic activities suggests that hypoxia directly increases histone methylation, leading to the induction or repression of many genes not through activating certain transcription factors but through directly inhibiting histone demethylases recruited to certain target genes.…”

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confidence: 99%

Hypoxic reprograming of H3K27me3 and H3K4me3 at the INK4A locus

et al. 2016

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Activation of Raf reduces the repressive histone mark H3K27me3 at the INK4a locus by inducing the H3K27me3 demethylase JMJD3. During hypoxia, the catalyitc activity of JMJD3 is reduced due to the limited availability of O 2 as a substrate. In our study, we found that hypoxia prevented Raf-induced JMJD3 from demethylating H3K27me3 at the INK4a locus. Nonetheless, hypoxia did not prevent Raf signaling from inducing INK4a mRNA. Interestingly, we found that hypoxia strongly enhanced the active histone mark H3K4me3 at the INK4a locus by inhibiting the H3K4me3 demethylases JARID1A and JARID1B. Therefore, this study demonstrates that the O 2 concentration in the microenvironment differentially affects the repressive methylation on K27 and the activating methylation on K4 at the INK4a locus by inhibiting the H3K27me3 and H3K4me3 demethylases.

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confidence: 99%

Hypoxic reprograming of H3K27me3 and H3K4me3 at the INK4A locus

et al. 2016

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“…There are two distinct families of mammalian histone demethylases with a growing number of their members often showing a functional overlap. Among them, LSD1 (also known as KDM1A) catalyzes demethylation of H3K4me1, H3K4me2, H3K9me1 and H3K9me2, and KDM2A demethylates H3K36me1 and H3K36me2 (Kooistra and Helin, 2012). These enzymes are thus part of the silencing machinery involved in chromatin organization inside the nucleus.…”

Section: Introductionmentioning

confidence: 99%

Chromatin organization at the nuclear periphery as revealed by image analysis of structured illumination microscopy data

Fišerová

Efenberková

Sieger

et al. 2017

Journal of Cell Science

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The nuclear periphery (NP) plays a substantial role in chromatin organization. Heterochromatin at the NP is interspersed with active chromatin surrounding nuclear pore complexes (NPCs); however, details of the peripheral chromatin organization are missing. To discern the distribution of epigenetic marks at the NP of HeLa nuclei, we used structured illumination microscopy combined with a new MATLAB software tool for automatic NP and NPC detection, measurements of fluorescent intensity and statistical analysis of measured data. Our results show that marks for both active and nonactive chromatin associate differentially with NPCs. The incidence of heterochromatin marks, such as H3K27me2 and H3K9me2, was significantly lower around NPCs. In contrast, the presence of marks of active chromatin such as H3K4me2 was only decreased very slightly around the NPCs or not at all (H3K9Ac). Interestingly, the histone demethylases LSD1 (also known as KDM1A) and KDM2A were enriched within the NPCs, suggesting that there was a chromatinmodifying mechanism at the NPCs. Inhibition of transcription resulted in a larger drop in the distribution of H1, H3K9me2 and H3K23me2, which implies that transcription has a role in the organization of heterochromatin at the NP.

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“…Chromatin could change in a gene-specific manner without a direct correlation to TF occupancy levels of expression. The H3K4me2 mark is usually associated with actively transcribed genes and positioned around the TSS and the promoter area, 47 and H3K9me2 is associated with gene silencing, especially when the mark is widespread along the gene. H3K9me2 can also be associated with openness/ gene activity when present at the 5' region of a gene 47 and can reflect changes elicited by DNA damage responses.…”

Section: Methodsmentioning

confidence: 99%

“…The H3K4me2 mark is usually associated with actively transcribed genes and positioned around the TSS and the promoter area, 47 and H3K9me2 is associated with gene silencing, especially when the mark is widespread along the gene. H3K9me2 can also be associated with openness/ gene activity when present at the 5' region of a gene 47 and can reflect changes elicited by DNA damage responses. 48,49 p53 and ER have been functionally and physically related to proteins involved in chromatin methyl mark changes, such as G9a and LSD1.…”

Section: Methodsmentioning

confidence: 99%