A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation

Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene -regulatory sequences such as promoters and enhancers. Here we identify an evolutionarily conserved factor, BRWD2/PHIP, which colocalizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, a...

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Published in:Genes & development 2017-10, Vol.31 (19), p.2003-2014
Main Authors: Morgan, Marc A J, Rickels, Ryan A, Collings, Clayton K, He, Xiaolin, Cao, Kaixiang, Herz, Hans-Martin, Cozzolino, Kira A, Abshiru, Nebiyu A, Marshall, Stacy A, Rendleman, Emily J, Sze, Christie C, Piunti, Andrea, Kelleher, Neil L, Savas, Jeffrey N, Shilatifard, Ali
Format: Article
Language:English
Subjects:
Acetylation
Animals
CRISPR-Cas Systems
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Enhancer Elements, Genetic
Epigenesis, Genetic
Gene Expression Regulation
Gene Knockout Techniques
Histone Methyltransferases
Histone-Lysine N-Methyltransferase - metabolism
Histones - metabolism
Humans
Methylation
Mice
Promoter Regions, Genetic
Protein Binding - genetics
Research Paper
Transcription Factors - genetics
Transcription Factors - metabolism
Tudor Domain
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Summary:Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene -regulatory sequences such as promoters and enhancers. Here we identify an evolutionarily conserved factor, BRWD2/PHIP, which colocalizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, and Biochemical analysis of BRWD2 demonstrated an association with the Cullin-4-RING ubiquitin E3 ligase-4 (CRL4) complex, nucleosomes, and chromatin remodelers. BRWD2/PHIP binds directly to H3K4 methylation through a previously unidentified chromatin-binding module related to Royal Family Tudor domains, which we named the CryptoTudor domain. Using CRISPR-Cas9 genetic knockouts, we demonstrate that COMPASS H3K4 methyltransferase family members differentially regulate BRWD2/PHIP chromatin occupancy. Finally, we demonstrate that depletion of the single homolog dBRWD3 results in altered gene expression and aberrant patterns of histone H3 Lys27 acetylation at enhancers and promoters, suggesting a cross-talk between these chromatin modifications and transcription through the BRWD protein family.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.305201.117