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Series GSE130091 Query DataSets for GSE130091
Status Public on Apr 20, 2019
Title Selective binding of the PHD6 finger of MLL4 to histone H4K16ac links MLL4 and MOF
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Histone methyltransferase MLL4 is centrally involved in transcriptional regulation and is often mutated in human diseases, including cancer and developmental disorders. MLL4 contains a catalytic SET domain that mono-methylates histone H3K4 and seven PHD fingers of unclear function. Here, we identify the PHD6 finger of MLL4 (MLL4-PHD6) as the first selective reader of the epigenetic modification H4K16ac. The solution NMR structure of MLL4-PHD6 in complex with a H4K16ac peptide along with binding and mutational analyses reveal unique mechanistic features underlying recognition of H4K16ac. Genomic studies show that one third of MLL4 chromatin binding sites overlap with H4K16ac-enriched regions in vivo and that MLL4 occupancy in a set of genomic targets depends on the acetyltransferase activity of MOF, a H4K16ac-specific acetyltransferase. The recognition of H4K16ac is conserved in the PHD7 finger of paralogous MLL3. Together, our findings highlight a novel acetyllysine reader and suggest that selective targeting of H4K16ac by MLL4 provides a direct functional link between MLL4, MOF and H4K16 acetylation.
 
Overall design Histone H3K4 mono-methyltransferase MLL4 and histone modifications (histone H4K16ac) by ChIP-seq in brown preadipocytes in culture.
 
Contributor(s) Younghoon J, Ji-Eun L, Kai G
Citation(s) 31127101
Submission date Apr 19, 2019
Last update date Jun 19, 2019
Contact name Kai Ge
E-mail(s) kai.ge@nih.gov
Phone 301-451-1998
Organization name NIH
Department NIDDK
Street address 10 Center Dr Rm 8N307
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (12)
GSM3731757 Mof_CreER_Vec_D-3_Mock_MLL4
GSM3731758 Mof_CreER_WT_rMof_D-3_4OHT_MLL4
GSM3731759 Mof_CreER_Vec_D-3_4OHT_Input
Relations
BioProject PRJNA533821
SRA SRP193112

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
GSE130091_RAW.tar 10.8 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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