Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells
Bo Wen,Hao Wu,Hao Wu,Yoichi Shinkai,Rafael A. Irizarry,Rafael A. Irizarry,Andrew P. Feinberg +6 more
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TLDR
It is found that differentiated tissues show surprisingly large K9-modified regions (up to 4.9 Mb), which are large organized chromatin K9 modifications (LOCKs) and may provide a cell type–heritable mechanism for phenotypic plasticity in development and disease.Abstract:
Higher eukaryotes must adapt a totipotent genome to specialized cell types with stable but limited 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) and find that differentiated tissues show surprisingly large K9-modified regions (up to 4.9 Mb). These regions are highly conserved between human and mouse and are differentiation specific, covering only approximately 4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, approximately 46% in liver and approximately 10% in brain. These modifications require histone methyltransferase G9a and are inversely related to expression of genes within the regions. We term these regions large organized chromatin K9 modifications (LOCKs). LOCKs are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease.read more
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Topological domains in mammalian genomes identified by analysis of chromatin interactions
Jesse R. Dixon,Siddarth Selvaraj,Siddarth Selvaraj,Feng Yue,Audrey Kim,Yan-Yan Li,Yin-Zhong Shen,Ming Hu,Jun Liu,Bing Ren,Bing Ren +10 more
TL;DR: It is found that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
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Epigenetics in Cancer
TL;DR: The current understanding of alterations in the epigenetic landscape that occur in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, including the cancer stem cell model, and the potential use of this knowledge in designing more effective treatment strategies are discussed.
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Spatial partitioning of the regulatory landscape of the X-inactivation centre
Elphège P. Nora,Bryan R. Lajoie,Edda G. Schulz,Luca Giorgetti,Luca Giorgetti,Luca Giorgetti,Ikuhiro Okamoto,Ikuhiro Okamoto,Ikuhiro Okamoto,Nicolas Servant,Nicolas Servant,Nicolas Servant,Tristan Piolot,Tristan Piolot,Tristan Piolot,Nynke L. van Berkum,Johannes Meisig,John W. Sedat,Joost Gribnau,Emmanuel Barillot,Emmanuel Barillot,Emmanuel Barillot,Nils Blüthgen,Job Dekker,Edith Heard,Edith Heard,Edith Heard +26 more
TL;DR: In addition to uncovering a new principle of cis-regulatory architecture of mammalian chromosomes, this study sets the stage for the full genetic dissection of the mouse X-inactivation centre.
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Charting histone modifications and the functional organization of mammalian genomes
Vicky Weijie Zhou,Alon Goren,Alon Goren,Alon Goren,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +6 more
TL;DR: A selection of recent studies that have probed histone modifications and successive layers of chromatin structure in mammalian genomes, the patterns that have been identified and future directions for research are reviewed.
Journal ArticleDOI
Increased methylation variation in epigenetic domains across cancer types
Kasper D. Hansen,Winston Timp,Winston Timp,Héctor Corrada Bravo,Héctor Corrada Bravo,Sarven Sabunciyan,Benjamin Langmead,Benjamin Langmead,Oliver G. McDonald,Bo Wen,Hao Wu,Yun Liu,Dinh Diep,Eirikur Briem,Kun Zhang,Rafael A. Irizarry,Rafael A. Irizarry,Andrew P. Feinberg +17 more
TL;DR: Stochastic methylation variation of the same cDMRs, distinguishing cancer from normal tissue, is shown in colon, lung, breast, thyroid and Wilms' tumors, with intermediate variation in adenomas.
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TL;DR: The results indicate that euchromatic H3-K9 methylation regulated by G9a is essential for early embryogenesis and is involved in the transcriptional repression of developmental genes.
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