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Series GSE199438 Query DataSets for GSE199438
Status Public on Apr 23, 2023
Title Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The ASH1L lysine methyltransferase plays a critical role in development and is frequently dysregulated in cancer and neurodevelopmental diseases. ASH1L catalyzes mono- and dimethylation of histone H3K36 and contains a set of uncharacterized domains. Here, we report the structure-function relationships of the C-terminal cassette of ASH1L encompassing a bromodomain (BD), a PHD finger and a bromo-associated homology (BAH) domain and show that ASH1L co-localizes with H3K4me3 but not with H3K36me2 at transcription start sites genome-wide and is involved in embryonic stem cell differentiation and transcriptional regulation of differentiation marker genes. Our crystal and NMR structural data provide mechanistic details for the recognition of H3K4me3 by PHD, the DNA binding activities of BD and BAH, and crosstalk among these domains. We show that the PHD-H3K4me3 interaction is inhibitory to the catalytic activity of ASH1L and that the DNA binding function of BAH is necessary for ASH1L engagement with the nucleosome. Our findings suggest a mechanism by which the C-terminus of ASH1L associates with chromatin and provide molecular and structural insights that are essential in therapeutic targeting of ASH1L.
 
Overall design ChIP-Seq of Ash1l and control in Retinoic Acid differentiated mouse ES cells
 
Contributor(s) Sharma R, Vann KR, Kutateladze TG
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Submission date Mar 25, 2022
Last update date Apr 25, 2023
Contact name Rajal Sharma
E-mail(s) rajal.sharma@mssm.edu
Organization name ISMMS
Street address 1425 Madison Ave., Room 16-52
City New York
State/province NY
ZIP/Postal code 10029
Country USA
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (2)
GSM5973022 Ash1l_mES
GSM5973023 Input_mES
Relations
BioProject PRJNA820002

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE199438_RAW.tar 500.1 Mb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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