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| Status |
Public on Jun 24, 2012 |
| Title |
Diverse epigenetic strategies interact to control epidermal differentiation [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
It is becoming clear that interconnected functional gene networks, rather than single genes in isolation, govern stem cell self-renewal and differentiation. To identify potential epigenetic networks that impact on human epidermal stem cells we performed siRNA based genetic screens for 332 chromatin modifiers. We developed a Bayesian mixture model to predict putative functional interactions between those epigenetic modifiers that regulated differentiation. This allowed us to discover a network of genetic interactions involving EZH2, UHRF1 (both known to regulate epidermal self-renewal), ING5 (a MORF complex component), BPTF and SMARCA5 (NURF complex components). Genome-wide localisation and global mRNA expression analysis revealed that these factors impact two distinct but functionally related gene sets, including integrin extracellular matrix receptors that mediate anchorage of epidermal stem cells to their niche. Using a competitive epidermal reconstitution assay we confirmed that ING5, BPTF, SMARCA5, EZH2 and UHRF1 control differentiation under physiological conditions. Thus, regulation of distinct gene expression programs through the interplay between diverse epigenetic strategies protects epidermal stem cells from differentiation.
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| |
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| Overall design |
Examination of genome-wide localisation of ING5 in primary human keratinocytes
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| Contributor(s) |
Mulder KW, Watt FM |
| Citation missing |
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| Submission date |
Dec 19, 2011 |
| Last update date |
Dec 03, 2018 |
| Contact name |
Chandra Chilamakuri |
| E-mail(s) |
datasubmissions@cruk.cam.ac.uk
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| Organization name |
Cancer Research UK Cambridge Institute
|
| Street address |
Robinson Way
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 0RE |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE34558 |
Diverse epigenetic strategies interact to control epidermal differentiation |
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| Relations |
| BioProject |
PRJNA156425 |
