|
| Status |
Public on Apr 12, 2017 |
| Title |
GRHL3 binding and the enhancer landscape are reorganized during transitions between different functional states of epidermal keratinocytes [siREST-proliferation] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The genomic mechanisms underlying progressive, irreversible cell lineage commitments and differentiation, which include large scale chromatin re-organization, transcription factor binding, and chromatin modifications, have been well defined. However, we know little about the chromatin changes during transitions between transient cell states such as cell migration. Here we demonstrate the formation of unique complements of typical enhancers and super-enhancers as human progenitor keratinocytes either differentiate or migrate. Unique super-enhancers for each cellular state are linked to gene expression that confer functions associated with each cell state, and sequence variants associated with skin diseases are enriched within super-enhancers. GRHL3, a factor that promotes both differentiation and migration, exhibits prominent super-enhancer interactions in differentiating keratinocytes, while during migration, it preferentially binds to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Of note, GRHL3 also represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Thus, coordinated GRHL3 binding and enhancer rearrangements regulate the functional states of keratinocytes.
|
| |
|
| Overall design |
pooled siRNA was used to knockdown REST in duplicate, with 2 scramble siRNA control replicates. Cells were collected 72 hours later. RNA was extracted and submitted for microarray.
|
| |
|
| Contributor(s) |
Herndon Klein R, Andersen B |
| Citation(s) |
28445475 |
| |
| Submission date |
Feb 03, 2017 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Bogi Andersen |
| Organization name |
University of California, Irvine
|
| Department |
Medicine
|
| Lab |
Andersen
|
| Street address |
839 Health Sciences Dr.
|
| City |
Irvine |
| State/province |
CA |
| ZIP/Postal code |
92697 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (4)
|
| GSM2476169 |
scramble control replicate 1 NHEK [siREST-proliferation] |
| GSM2476170 |
scramble control replicate 2 NHEK [siREST-proliferation] |
| GSM2476171 |
siREST replicate 1 NHEK [siREST-proliferation] |
| GSM2476172 |
siREST replicate 2 NHEK [siREST-proliferation] |
|
| This SubSeries is part of SuperSeries: |
| GSE94471 |
GRHL3 binding and the enhancer landscape are reorganized during transitions between different functional states of epidermal keratinocytes |
|
| Relations |
| BioProject |
PRJNA369794 |
Less...
More...