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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 cis-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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710144/ https://www.ncbi.nlm.nih.gov/pubmed/29089422 http://dx.doi.org/10.1101/gad.305201.117 |
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author | 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 |
author_facet | 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 |
author_sort | Morgan, Marc A.J. |
collection | PubMed |
description | Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene cis-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 Drosophila. 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 Drosophila 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. |
format | Online Article Text |
id | pubmed-5710144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57101442018-04-01 A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation 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 Genes Dev Research Paper Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene cis-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 Drosophila. 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 Drosophila 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. Cold Spring Harbor Laboratory Press 2017-10-01 /pmc/articles/PMC5710144/ /pubmed/29089422 http://dx.doi.org/10.1101/gad.305201.117 Text en © 2017 Morgan et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper 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 A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation |
title | A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation |
title_full | A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation |
title_fullStr | A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation |
title_full_unstemmed | A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation |
title_short | A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation |
title_sort | cryptic tudor domain links brwd2/phip to compass-mediated histone h3k4 methylation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710144/ https://www.ncbi.nlm.nih.gov/pubmed/29089422 http://dx.doi.org/10.1101/gad.305201.117 |
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