Dataset Information

Combinatorial patterns of histone acetylations and methylations in the human genome.

ABSTRACT: Histones are characterized by numerous posttranslational modifications that influence gene transcription. However, because of the lack of global distribution data in higher eukaryotic systems, the extent to which gene-specific combinatorial patterns of histone modifications exist remains to be determined. Here, we report the patterns derived from the analysis of 39 histone modifications in human CD4(+) T cells. Our data indicate that a large number of patterns are associated with promoters and enhancers. In particular, we identify a common modification module consisting of 17 modifications detected at 3,286 promoters. These modifications tend to colocalize in the genome and correlate with each other at an individual nucleosome level. Genes associated with this module tend to have higher expression, and addition of more modifications to this module is associated with further increased expression. Our data suggest that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation.

SUBMITTER: Wang Z

PROVIDER: S-EPMC2769248 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Combinatorial patterns of histone acetylations and methylations in the human genome.

Wang Zhibin Z Zang Chongzhi C Rosenfeld Jeffrey A JA Schones Dustin E DE Barski Artem A Cuddapah Suresh S Cui Kairong K Roh Tae-Young TY Peng Weiqun W Zhang Michael Q MQ Zhao Keji K

Nature genetics 20080615 7

Histones are characterized by numerous posttranslational modifications that influence gene transcription. However, because of the lack of global distribution data in higher eukaryotic systems, the extent to which gene-specific combinatorial patterns of histone modifications exist remains to be determined. Here, we report the patterns derived from the analysis of 39 histone modifications in human CD4(+) T cells. Our data indicate that a large number of patterns are associated with promoters and e ...[more]

PMID: 18552846

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Project description:Rationale: Manipulation of the gut microbiome can prevent pathologic bone loss. However, the effects of probiotics on mitochondrial epigenetic remodeling and skeletal homeostasis in the high-fat diet (HFD)-linked obesity remains to be explored. Here, we examined the impact of probiotics supplementation on mitochondrial biogenesis and bone homeostasis through the histone methylation mechanism in HFD fed obese mice. Methods: 16S rRNA gene sequencing was performed to study the microbiota composition in the gut and microbial dysbiosis in obese mouse model. High resolution (microPET/CT) imaging was performed to demonstrate the obese associated colonic inflammation. Obese-associated upregulation of target miRNA in osteoblast was investigated using a microRNA qPCR array. Osteoblastic mitochondrial mass was evaluated using confocal imaging. Overexpression of mitochondrial transcription factor (Tfam) was used to investigate the glycolysis and mitochondrial bioenergetic metabolism using Tfam-transgenic (Tg) mice fed on HFD. The bone formation and mechanical strength was evaluated by microCT analysis and three-point bending analysis. Results: High-resolution imaging (µ-CT) and mechanical testing revealed that probiotics induced a significant increase of trabecular bone volume and bone mechanical strength respectively in obese mice. Probiotics or Indole-3-propionic acid (IPA) treatment directly to obese mice, prevents gut inflammation, and improved osteoblast mineralization. Mechanistically, probiotics treatment increases mitochondrial transcription factor A (Tfam) expression in osteoblasts by promoting Kdm6b/Jmjd3 histone demethylase, which inhibits H3K27me3 epigenetic methylation at the Tfam promoter. Furthermore, Tfam-transgenic (Tg) mice, fed with HFD, did not experience obesity-linked reduction of glucose uptake, mitochondrial biogenesis and mineralization in osteoblasts. Conclusions: These results suggest that the probiotics mediated changes in the gut microbiome and its derived metabolite, IPA are potentially be a novel agent for regulating bone anabolism via the gut-bone axis.

Dataset Information

Combinatorial patterns of histone acetylations and methylations in the human genome.

Publications

Combinatorial patterns of histone acetylations and methylations in the human genome.

Similar Datasets

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