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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
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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.
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Overall design |
Histone H3K4 mono-methyltransferase MLL4 and histone modifications (histone H4K16ac) by ChIP-seq in brown preadipocytes in culture.
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Contributor(s) |
Younghoon J, Ji-Eun L, Kai G |
Citation(s) |
31127101 |
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Submission date |
Apr 19, 2019 |
Last update date |
Jun 19, 2019 |
Contact name |
Kai Ge |
E-mail(s) |
kai.ge@nih.gov
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Phone |
301-451-1998
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Organization name |
NIH
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Department |
NIDDK
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Street address |
50 South Dr Rm 4154
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA533821 |
SRA |
SRP193112 |