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| Status |
Public on Jan 18, 2009 |
| Title |
Large organized chromatin K9-modifications (LOCKs) distinguish differentiated from embryonic stem cells |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Wen B, Wu H, Shinkai Y, Irizarry RA, Feinberg AP |
| Citation(s) |
19151716 |
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| Submission date |
Nov 03, 2008 |
| Last update date |
Jun 05, 2012 |
| Contact name |
Andrew P. Feinberg |
| E-mail(s) |
afeinberg@jhu.edu
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| Organization name |
Johns Hopkins University
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| Department |
Center for Epigenetics and Department of Medicine
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| Street address |
855 N. Wolfe Street
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21212 |
| Country |
USA |
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| Platforms (8)
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| GPL7513 |
NimbleGen human (hg17) ENCODE tiling array |
| GPL7520 |
Custom human (hg17) imprinting tiling array |
| GPL7521 |
NimbleGen mouse mm7 ENCODE tiling array (385k) |
| GPL7522 |
Custom mouse (mm8) imprinting tiling array |
| GPL7523 |
NimbleGen mouse (mm8) whole genome tiling array 1 of 4 [2007-08-17_MM8_Economy_01] |
| GPL7524 |
NimbleGen mouse (mm8) whole genome tiling array 2 of 4 [2007-08-17_MM8_Economy_02] |
| GPL7525 |
NimbleGen mouse (mm8) whole genome tiling array 3 of 4 [2007-08-17_MM8_Economy_03] |
| GPL7526 |
NimbleGen mouse (mm8) whole genome tiling array 4 of 4 [2007-08-17_MM8_Economy_04] |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA110043 |
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