Large organized chromatin K9-modifications (LOCKs) distinguish differentiated from embryonic stem cells
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PROVIDER: PRJNA110043 | ENA |
REPOSITORIES: ENA
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Project description:Higher eukaryotes must adapt a totipotent genome to specialized cell types with a stable but limited repertoire of functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes. We have taken a genome-wide view of histone H3 lysine-9 dimethylation (H3K9Me2). We find that differentiated tissues exhibit surprisingly large K9-modified regions (up to 4.9 Mb), that are highly conserved between human and mouse, and differentiation-specific, covering only ~4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, ~46% in liver and ~10% in brain. They require histone methyltransferase G9a, and are inversely related to expression of genes within them, and we term them Large Organized Chromatin K9-modifications (LOCKs). LOCKs are are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease.
2009-01-18 | GSE13445 | GEO
Project description:Higher eukaryotes must adapt a totipotent genome to specialized cell types with a stable but limited repertoire of functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes. We have taken a genome-wide view of histone H3 lysine-9 dimethylation (H3K9Me2). We find that differentiated tissues exhibit surprisingly large K9-modified regions (up to 4.9 Mb), that are highly conserved between human and mouse, and differentiation-specific, covering only ~4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, ~46% in liver and ~10% in brain. They require histone methyltransferase G9a, and are inversely related to expression of genes within them, and we term them Large Organized Chromatin K9-modifications (LOCKs). LOCKs are are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease. Chromatin was isolated without sonication or formalin cross linking, by digested with micrococcal nuclease, and then chromatin immunoprecipitation was performed with an antibody specific to H3K9Me2. ChIP and input DNA were amplified, labeled by Cy5 and Cy3 respectively, and hybridized to NimbleGen tilling arrays.
2009-01-17 | E-GEOD-13445 | biostudies-arrayexpress
Project description:Histone modification H3K27me3 is crucial for normal development and is implicated in many diseases, including cancer. H3K27me3 peaks form clusters called Large Organized Chromatin Lysine Domains (LOCKs) that span several hundred kilobases. In this study, we identified H3K27me3 LOCKs in 109 normal samples from the Roadmap project and categorized them into long and short LOCKs. Long LOCKs are preferentially linked to developmental functions, while short LOCKs strongly repress gene expression and are enriched in poised promoters. By examining LOCK distribution in common PMDs (Partially Methylated Domains) and HMDs (Highly Methylated Domains), we discovered that long LOCKs are primarily located in short-PMDs (S-PMDs). Oncogenes within S-PMDs are often covered by long LOCKs, exerting the strongest repression. Analyzing LOCKs in esophageal squamous cell carcinoma (ESCC) and breast cancer (BRCA) cell lines and their normal counterparts, we observed a transition of long LOCK distribution from S-PMDs, to intermediate-PMDs (I-PMDs) and long-PMDs (L-PMDs). Interestingly, a substantial subset of tumor-gain long LOCKs within I-PMDs (23%-40%) and L-PMDs (28%-61%) in BRCA exhibit reduced H3K9me3 modification, indicating H3K27me3 compensates for H3K9me3 loss in tumor. Besides, genes upregulated upon short LOCK loss in tumors are frequently poised promoter genes in normal cells and are transcriptionally regulated by ETS1. These results highlight the role of H3K27me3 LOCKs in various epigenomic contexts and their involvement in cancer biology, revealing underlying epigenetic mechanisms.
2025-01-18 | GSE270715 | GEO
Project description:Chromatin Immunoprecipitation of centromeric protein A, histone3 K4 and K9 modifications, HP1a and HP1g
2010-02-27 | E-TABM-705 | biostudies-arrayexpress
Project description:The human genome is partitioned into a collection of genomic features, inclusive of genes, transposable elements, lamina interacting regions, early replicating control elements and cis-regulatory elements, such as promoters, enhancers, and anchors of chromatin interactions. Uneven distribution of these features within chromosomes gives rise to clusters, such as topologically associating domains (TADs), lamina-associated domains, clusters of cis-regulatory elements or large organized chromatin lysine (K) domains (LOCKs). Here we show that LOCKs from diverse histone modifications discriminate primitive from differentiated cell types. Active LOCKs (H3K4me1, H3K4me3 and H3K27ac) cover a higher fraction of the genome in primitive compared to differentiated cell types while repressive LOCKs (H3K9me3, H3K27me3 and H3K36me3) do not. Active LOCKs in differentiated cells lie proximal to highly expressed genes while active LOCKs in primitive cells tend to be bivalent. Genes proximal to bivalent LOCKs are minimally expressed in primitive cells. Furthermore, bivalent LOCKs populate TAD boundaries and are preferentially bound by regulators of chromatin interactions, including CTCF, RAD21 and ZNF143. Together, our results argue that LOCKs discriminate primitive from differentiated cell populations.
| S-EPMC7820432 | biostudies-literature
Project description:Class switch recombination (CSR) involves a DNA rearrangement in the Ig heavy chain (IgH) gene that allows the same variable (V) region to be expressed with any one of the downstream constant region (C) genes to encode antibodies with many different effector functions. One hypothesis for how CSR is targeted to different C region genes is that histone modifications increase accessibility and/or recruit activation-induced cytosine deaminase (AID) and its associated processes to particular donor and recipient switch regions. In this work, we identified H3 acetyl K9 and H3 trimethyl K9 as histone modifications that correlate with the recombining pair of donor and recipient switch regions. The appearance of H3 trimethyl K9 is surprising because usually it is thought to mark silent genes and heterochromatin. Nevertheless, the time course of appearance of these histone modifications, the regions in IgH they associate with, and their appearance independent of AID damage suggest that both modifications play a role in targeting CSR.
| S-EPMC2654022 | biostudies-literature
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