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Status |
Public on Sep 04, 2015 |
Title |
Pre-patterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Dynamic interactions of nuclear lamins with chromatin through so-called lamin-associated domains (LADs) contribute to spatial arrangements of the genome. Here, we provide evidence for pre-patterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified by the nutrient sensor O-linked N-acetylglucosamine (H2BGlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving (i) a spreading of lamin A/C-chromatin interactions during the transition from progenitor cell proliferation to cell cycle arrest, and (ii) a genome-scale redistribution these interactions through a process of LAD ‘exchange’ within hours of adipogenic induction. Chromatin state modeling reveals that lamin A/C LADs can be found both in active and repressive chromatin contexts which can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs non-randomly on GADs, consisting of megabase-size intergenic and repressive chromatin domains. Accordingly, while pre-differentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Moreover, release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional upregulation after adipogenic induction, and with concordant downstream elevations in H2BGlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic pre-patterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification.
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Overall design |
Examination of LMNA and H2BGlcNAc binding in ASCs across differentiation
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Contributor(s) |
Shah A, Rønningen T, Oldenburg A, Delbarre E, Moskaug JO, Collas P |
Citation(s) |
26359231 |
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Submission date |
Nov 17, 2014 |
Last update date |
May 15, 2019 |
Contact name |
Philippe Collas |
Organization name |
University of Oslo
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Department |
Institute of Basic Medical Sciences
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Street address |
PO Box 1112 Blindern
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City |
Oslo |
ZIP/Postal code |
0317 |
Country |
Norway |
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Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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Samples (12)
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Relations |
BioProject |
PRJNA267547 |
SRA |
SRP049946 |
Supplementary file |
Size |
Download |
File type/resource |
GSE63346_RAW.tar |
267.2 Mb |
(http)(custom) |
TAR (of BED, BW, CSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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