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

Marc Alard Morgan, Ryan A. Rickels, Clayton K. Collings, Xiaolin He, Kaixiang Cao, Hans Martin Herz, Kira A. Cozzolino, Nebiyu A. Abshiru, Stacy A. Marshall, Emily J. Rendleman, Christie C. Sze, Andrea Piunti, Neil L Kelleher, Jeffrey Nicholas Savas, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2003-2014
Number of pages12
JournalGenes and Development
Volume31
Issue number19
DOIs
StatePublished - Oct 1 2017

Fingerprint

Histones
Methylation
Chromatin
Drosophila
Clustered Regularly Interspaced Short Palindromic Repeats
Cullin Proteins
Ubiquitin-Protein Ligases
Nucleosomes
Methyltransferases
Regulator Genes
Acetylation
Tudor Domain
Genome
Gene Expression
Proteins

Keywords

  • BRWD
  • COMPASS
  • H3K4
  • Histone methylation
  • PHIP
  • Tudor domain

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Morgan, Marc Alard ; 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 Nicholas ; Shilatifard, Ali. / A cryptic tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation. In: Genes and Development. 2017 ; Vol. 31, No. 19. pp. 2003-2014.
@article{241e1e4ce3df44388b3246b9b5613225,
title = "A cryptic tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation",
abstract = "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.",
keywords = "BRWD, COMPASS, H3K4, Histone methylation, PHIP, Tudor domain",
author = "Morgan, {Marc Alard} and Rickels, {Ryan A.} and Collings, {Clayton K.} and Xiaolin He and Kaixiang Cao and Herz, {Hans Martin} and Cozzolino, {Kira A.} and Abshiru, {Nebiyu A.} and Marshall, {Stacy A.} and Rendleman, {Emily J.} and Sze, {Christie C.} and Andrea Piunti and Kelleher, {Neil L} and Savas, {Jeffrey Nicholas} and Ali Shilatifard",
year = "2017",
month = "10",
day = "1",
doi = "10.1101/gad.305201.117",
language = "English (US)",
volume = "31",
pages = "2003--2014",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "19",

}

Morgan, MA, Rickels, RA, Collings, CK, He, X, Cao, K, Herz, HM, Cozzolino, KA, Abshiru, NA, Marshall, SA, Rendleman, EJ, Sze, CC, Piunti, A, Kelleher, NL, Savas, JN & Shilatifard, A 2017, 'A cryptic tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation', Genes and Development, vol. 31, no. 19, pp. 2003-2014. https://doi.org/10.1101/gad.305201.117

A cryptic tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation. / Morgan, Marc Alard; 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 Nicholas; Shilatifard, Ali.

In: Genes and Development, Vol. 31, No. 19, 01.10.2017, p. 2003-2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A cryptic tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation

AU - Morgan, Marc Alard

AU - Rickels, Ryan A.

AU - Collings, Clayton K.

AU - He, Xiaolin

AU - Cao, Kaixiang

AU - Herz, Hans Martin

AU - Cozzolino, Kira A.

AU - Abshiru, Nebiyu A.

AU - Marshall, Stacy A.

AU - Rendleman, Emily J.

AU - Sze, Christie C.

AU - Piunti, Andrea

AU - Kelleher, Neil L

AU - Savas, Jeffrey Nicholas

AU - Shilatifard, Ali

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

KW - BRWD

KW - COMPASS

KW - H3K4

KW - Histone methylation

KW - PHIP

KW - Tudor domain

UR - http://www.scopus.com/inward/record.url?scp=85032984999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032984999&partnerID=8YFLogxK

U2 - 10.1101/gad.305201.117

DO - 10.1101/gad.305201.117

M3 - Article

C2 - 29089422

AN - SCOPUS:85032984999

VL - 31

SP - 2003

EP - 2014

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 19

ER -