A histone H3.3K36M mutation in mice causes an imbalance of histone modifications and defects in chondrocyte differentiation

Abe, Shusaku; Nagatomo, Hiroaki; Sasaki, Hidetada; Ishiuchi, Takashi

doi:10.1080/15592294.2020.1841873

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…Histone H3.3 with a K36M substitution (H3.3K36M) was identified as an onco-histone that affects the global H3K36 methylation level through its inhibitory effect on histone H3K36 methyltransferases 17,[24][25][26] . While several studies reported that the mutation affects both H3K36me2 and H3K36me3 17,24,25,27,28 , we and others found that, in mouse tissues, H3.3K36M causes specific reduction of H3K36me2, possibly through its preferential effect on NSD1 and NSD2 21,22 , which catalyze H3K36me2 deposition. To determine the importance of H3K36me2 in shaping the CG methylation landscape of oocytes, we used conditional knock-in mice that we reported previously 22 : this mouse line expressed HAtagged H3.3K36M from the H3f3b locus in a Cre-dependent manner (Supplementary Fig.…”

Section: Loss Of H3k36me2 Causes Cg Hypomethylation In Mmrs Of Oocytescontrasting

confidence: 49%

“…To elucidate the H3K36me2 distribution in more detail, we performed ultra-low-input native chromatin immunoprecipitation sequencing (ULI-NChIP-seq) 20 (Supplementary Table 2). H3K36me2 was distributed in broad domains covering both genic and intergenic regions in FGOs, albeit with local changes, as observed in cultured cells and mouse tissues [21][22][23][24][25] (Fig. 1b).…”

Section: H3k36me2-enriched Regions Are Associated With Moderate Level...mentioning

confidence: 61%

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Histone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes

et al. 2022

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Establishment of the DNA methylation landscape of mammalian oocytes, mediated by the DNMT3A-DNMT3L complex, is crucial for reproduction and development. In mouse oocytes, high levels of DNA methylation occur exclusively in the transcriptionally active regions, with moderate to low levels of methylation in other regions. Histone H3K36me3 mediates the high levels of methylation in the transcribed regions; however, it is unknown which histone mark guides the methylation in the other regions. Here, we show that, in mouse oocytes, H3K36me2 is highly enriched in the X chromosome and is broadly distributed across all autosomes. Upon H3K36me2 depletion, DNA methylation in moderately methylated regions is selectively affected, and a methylation pattern unique to the X chromosome is switched to an autosome-like pattern. Furthermore, we find that simultaneous depletion of H3K36me2 and H3K36me3 results in global hypomethylation, comparable to that of DNMT3A depletion. Therefore, the two histone marks jointly provide the chromatin platform essential for guiding DNMT3A-dependent DNA methylation in mouse oocytes.

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Section: Loss Of H3k36me2 Causes Cg Hypomethylation In Mmrs Of Oocytescontrasting

confidence: 49%

Section: H3k36me2-enriched Regions Are Associated With Moderate Level...mentioning

confidence: 61%

Histone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes

et al. 2022

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“… 213 Following the oncohistone paradigm, the H3K36me2/3 PTMs are reduced due to the inability of specific methyltransferases, namely SETD2, NSD1-NSD3, to deposit their marks. 214 , 215 H3K36M reduces H3K36 methylation and increases nucleosome availability for PRC2 to deposit H3K27me3. 214 The genome-wide increase in this repressive mark then induces a PRC1 redeployment which overall dilutes PRC1 at its canonical binding sites, leading to de-repression of self-renewal genes 214 , 216 (Fig.…”

Section: Environmental Cues and Polycomb-dependent Oncogenesismentioning

confidence: 99%

Mechanisms of Polycomb group protein function in cancer

2022

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Cancer arises from a multitude of disorders resulting in loss of differentiation and a stem cell-like phenotype characterized by uncontrolled growth. Polycomb Group (PcG) proteins are members of multiprotein complexes that are highly conserved throughout evolution. Historically, they have been described as essential for maintaining epigenetic cellular memory by locking homeotic genes in a transcriptionally repressed state. What was initially thought to be a function restricted to a few target genes, subsequently turned out to be of much broader relevance, since the main role of PcG complexes is to ensure a dynamically choregraphed spatio-temporal regulation of their numerous target genes during development. Their ability to modify chromatin landscapes and refine the expression of master genes controlling major switches in cellular decisions under physiological conditions is often misregulated in tumors. Surprisingly, their functional implication in the initiation and progression of cancer may be either dependent on Polycomb complexes, or specific for a subunit that acts independently of other PcG members. In this review, we describe how misregulated Polycomb proteins play a pleiotropic role in cancer by altering a broad spectrum of biological processes such as the proliferation-differentiation balance, metabolism and the immune response, all of which are crucial in tumor progression. We also illustrate how interfering with PcG functions can provide a powerful strategy to counter tumor progression.

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“…It also promoted the cell proliferation, migration, invasion of endometrial carcinoma by through targeting MARK1 [28]. H3F3B plays the key role in the maturation and differentiation of chondrocyte [29] and serves as a target gene of miR-486-5p according to the report [30] and database analysis. However, whether miR-486-5p in uences the progression of microtia through targeting H3F3B is rarely explored in previous study.…”

Section: Discussionmentioning

confidence: 99%

MiR-486-5p represses chondrocyte multiplication but facilitates their deaths in congenital microtia through aiming at H3F3B

Liu¹,

Zhang²,

Dong³

et al. 2021

Preprint

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Background MicroRNAs have been reported to play important roles in the development of external ear. The present study was designed to explore the expression patterns and biological function of miR-486-5p in congenital microtia. Methods Cartilage tissue specimens were collected from congenital microtia cases who received reconstructive ear surgeries, while the normal cartilage tissues from other otology surgeries were adopted as normal controls. The relative expression of miR-486-5p was investigated by quantitative-real time polymerase chain reaction. The potential target of miR-486-5p was explored by TargetScanHuman 7.2 and dual-Luciferase reporter assay. MTT and flow cytometry assays were adopted to investigate cell proliferation and apoptosis, respectively. Results The expression of miR-486-5p was significantly up-regulated in microtia cartilage tissues. Knockdown of miR-486-5p in microtia chondrocytes enhanced proliferation and inhibited apoptosis. H3F3B might be a target of miR-486-5p, and miR-486-5p could regulate proliferation and apoptosis of microtia chondrocytes by targeting H3F3B. Moreover, the enforced expression of H3F3B could re-turned the function of miR-486-5p in microtia chondrocytes. Conclusion Up-regulation of miR-486-5p may inhibit microtia chondrocytes proliferation and promote apoptosis by targeting H3F3B.

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A histone H3.3K36M mutation in mice causes an imbalance of histone modifications and defects in chondrocyte differentiation

Cited by 9 publications

References 40 publications

Histone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes

Histone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes

Mechanisms of Polycomb group protein function in cancer

MiR-486-5p represses chondrocyte multiplication but facilitates their deaths in congenital microtia through aiming at H3F3B

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