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Cited by 140Genomics and Chromatin DynamicsEpigenetics and DNA MethylationCancer-related gene regulation

WRAD: enabler of the SET1-family of H3K4 methyltransferases

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Ernst, P., Vakoc, C. R.·2012·Briefings in Functional Genomics
DOI 10.1093/bfgp/els017PMC PMC3388306
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Abstract

Methylation of histone H3 at lysine 4 (H3K4) is a conserved feature of active chromatin catalyzed by methyltransferases of the SET1-family (SET1A, SET1B, MLL1, MLL2, MLL3 and MLL4 in humans). These enzymes participate in diverse gene regulatory networks with a multitude of known biological functions, including direct involvement in several human disease states. Unlike most lysine methyltransferases, SET1-family enzymes are only fully active in the context of a multi-subunit complex, which includes a protein module comprised of WDR5, RbBP5, ASH2L and DPY-30 (WRAD). These proteins bind in close proximity to the catalytic SET domain of SET1-family enzymes and stimulate H3K4 methyltransferase activity. The mechanism by which WRAD promotes catalysis involves elements of allosteric control and possibly the utilization of a second H3K4 methyltransferase active site present within WRAD itself. WRAD components also engage in physical interactions that recruit SET1-family proteins to target sites on chromatin. Here, the known molecular mechanisms through which WRAD enables the function of SET1-related enzymes will be reviewed.

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  • MLL4 exists in a multi-protein complex containing core components WDR5, ASH2L, RBBP5 and DPY30 and other complex-specific proteins such as PAGR1, KDM6A, NCOA6 and PAXIP1.

    “MLL4 exists in a multi-protein complex containing the core components WDR5, ASH2L, RBBP5 and DPY3038,39 and other complex-specific proteins, such as PAGR1 (previously known as PA1), KDM6A (UTX), NCOA6 and PAXIP1 (PTIP)37,40.”

    From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [39]

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Authors
Ernst, P., & Vakoc, C. R.
Affiliations
Dartmouth College (US)
Corresponding author
Vakoc, C. R.
ORCID
Venue
Briefings in Functional Genomics
Publisher
Oxford University Press (OUP)
Published
2012-05-01
Volume
11
Issue
3
Pages
217-226
ISSN
  • 2041-2647 (ISSN-L)
  • 2041-2649
  • 2041-2657
DOI
10.1093/bfgp/els017
PMC
PMC3388306
OpenAlex
W2124418801
Cited by
140
References
3
Citations by year
2026: 7 · 2025: 7 · 2024: 19 · 2023: 14 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 11 · 2018: 10 · 2017: 10 · 2016: 11 · 2015: 12 · 2014: 6 · 2013: 2 · 2012: 1
FWCI
0.64
Type
journal article
Language
en
Open access
Locations
  • Briefings in Functional Genomics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • F. M. Kirby Foundation
  • Don Monti Memorial Research Foundation
  • Edward P. Evans Foundation
  • National Heart, Lung, and Blood Institute (R01HL090036, HL090036)
  • National Cancer Institute (CA023108, P30CA023108)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Keywords
H3K4 methyltransferase, WDR5, RBBP5, ASH2L, SET domain, allosteric regulation, chromatin regulation, MLL1, KMT2D, MLL3, SET1A, chromatin recruitment
MeSH terms
Animals, Chromatin, Histones, Humans, Lysine, Methylation, Histone-Lysine N-Methyltransferase, Multiprotein Complexes

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