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| Status |
Public on Jul 20, 2018 |
| Title |
Nascent transcription of E14, PWWP2AKO, and PWWP2A/B DKO |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Transcriptional regulation by chromatin is a highly dynamic process directed through the recruitment and coordinated action of epigenetic modifiers and readers of these modifications. Using an unbiased proteomic approach to find interactors of H3K36me3, a modification enriched on active chromatin, here we identify PWWP2A and HDAC2 among the top interactors. PWWP2A and its paralog PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66α/β, and CHD3/4. PWWP2A competes with MBD3 for binding to MTA1, thus defining a new variant NuRD complex that is mutually exclusive with the MBD2/3-containing NuRD. In mESCs, PWWP2A/B is most enriched at highly transcribed genes. Loss of PWWP2A/B leads to increases in histone acetylation predominantly at highly expressed genes, accompanied by decreases in Pol II elongation. Collectively, these findings suggest a role for PWWP2A/B in regulating transcription through the fine-tuning of histone acetylation dynamics at actively transcribed genes.
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| Overall design |
In order to explore the influence of PWWP2A/B on nascent transcription, we isolated the 4sU-labelled nascent transcripts, followed by deep sequencing. Three cell lines, E14, PWWP2A KO, and PWWP2A/B double knockout, and three biological replicates.
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| Contributor(s) |
Zhang T, Wei G, Brockdorff N |
| Citation(s) |
30228260 |
| |
| Submission date |
Mar 20, 2018 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Guifeng Wei |
| E-mail(s) |
guifeng.wei@bioch.ox.ac.uk
|
| Organization name |
University of Oxford
|
| Department |
Department of Biochemistry
|
| Lab |
Brockdorff Lab
|
| Street address |
South Parks Road
|
| City |
Oxford |
| ZIP/Postal code |
OX1 3QU |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE112114 |
A variant NuRD complex containing PWWP2A/B excludes MBD2/3 and directs HDAC activity to regulate histone acetylation and RNA Pol II dynamics at active genes |
|
| Relations |
| BioProject |
PRJNA439319 |
| SRA |
SRP136127 |
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