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| Status |
Public on Apr 01, 2013 |
| Title |
The histone chaperone Spt6 coordinates histone H3K27 demethylation to regulate gene expression and myogenesis |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Histone chaperones affect chromatin structure and gene expression through interaction with histones and RNA polymerase II (PolII). Here, we report that the histone chaperone Spt6 counteracts H3K27me3, an epigenetic mark deposited by the Polycomb Repressive Complex 2 (PRC2) and associated with transcriptional repression. We found that Spt6 is required for proper engagement and function of the H3K27 demethylase KDM6A (UTX) on muscle genes and regulates muscle gene expression and cell differentiation. ChIP-Seq experiments revealed an extensive genome-wide overlap of Spt6, PolII and KDM6A at transcribed regions that are devoid of H3K27me3. Mammalian cells and zebrafish embryos with reduced Spt6 display increased H3K27me3 and diminished expression of the master regulator MyoD, resulting in myogenic differentiation defects. As a confirmation for an antagonistic relationship between Spt6 and H3K27me3, inhibition of PRC2 permits MyoD re-expression in myogenic cells with reduced Spt6. Our data indicate that, through cooperation with PolII and KDM6A, Spt6 orchestrates removal of H3K27me3, thus effectively controlling developmental gene expression and cell differentiation.
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| Overall design |
Examination of Spt6 and KDM6A levels in a skeletal muscle cells at various developmental stages
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| Contributor(s) |
Wang AH, Zare H, Mousavi K, Sartorelli V |
| Citation(s) |
23503590 |
| Submission date |
Feb 06, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Hossein Zare |
| E-mail(s) |
hzare@mail.nih.gov
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| Organization name |
NIH
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| Street address |
5o South Dr #1347
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| City |
Bethesda |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA188719 |
| SRA |
SRP018432 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44119_RAW.tar |
1.0 Gb |
(http)(custom) |
TAR (of BED, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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