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Chromatin regulation of transcriptional enhancers and cell fate by the Sotos syndrome gene NSD1 [TT-Seq]

UID: 10902

Author(s): Sun, Zhen*, Helin, Kristian* * MSK affiliated

Description
Summary from GEO:

"Nuclear-receptor-binding SET-domain protein 1 (NSD1), a methyltransferase that catalyzes H3K36me2, is essential for mammalian development and frequently dysregulated in diseases, including Sotos syndrome. Despite impacts of H3K36me2 on H3K27me3 and DNA methylation, a direct role of NSD1 in transcriptional regulation remains largely unknown. Here, we show that NSD1 and H3K36me2 are enriched at cis-regulatory elements, particularly enhancers. NSD1 enhancer association is conferred by a tandem quadruple PHD-PWWP module, which recognizes p300-catalyzed H3K18ac. By combining acute NSD1 depletion with time-resolved epigenomic and nascent transcriptomic analyses, we demonstrate that NSD1 promotes enhancer-dependent gene transcription by facilitating RNA polymerase II pause release. Notably, NSD1 can act as a transcriptional coactivator independent of its catalytic activity. Moreover, NSD1 enables activation of developmental transcriptional programs associated with Sotos syndrome pathophysiology and controls ESC multilineage differentiation. Collectively, we have identified NSD1 as an enhancer-acting transcriptional coactivator that contributes to cell fate transition and Sotos syndrome development."

Overall design

"TT-seq was performed with NSD1-dTAG mESCs after 0, 1, and 6h of dTAG-13 treatment."
Subject of Study
Subject(s)
Access via GEO


Accession #: GSE236029

Access via BioProject


Accession #: PRJNA988460

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus and BioProject databases provides open access to these files.
Associated Publications
Equipment Used
Illumina NextSeq 550
Dataset Format(s)
TAR, BIGWIG
Dataset Size
150.6 MB (BIGWIG), 160.7 MB (BIGWIG), 136.5 MB (BIGWIG), 515.7 MB (TAR)
Data Catalog Record Updated
2023-10-09