Cited by 1,091Genomics and Chromatin DynamicsEpigenetics and DNA MethylationCancer-related gene regulation

The COMPASS Family of Histone H3K4 Methylases: Mechanisms of Regulation in Development and Disease Pathogenesis

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Shilatifard, Ali·2012·Annual Review of Biochemistry

Abstract

The Saccharomyces cerevisiae Set1/COMPASS was the first histone H3 lysine 4 (H3K4) methylase identified over 10 years ago. Since then, it has been demonstrated that Set1/COMPASS and its enzymatic product, H3K4 methylation, is highly conserved across the evolutionary tree. Although there is only one COMPASS in yeast, Drosophila possesses three and humans bear six COMPASS family members, each capable of methylating H3K4 with nonredundant functions. In yeast, the histone H2B monoubiquitinase Rad6/Bre1 is required for proper H3K4 and H3K79 trimethylations. The machineries involved in this process are also highly conserved from yeast to human. In this review, the process of histone H2B monoubiquitination-dependent and -independent histone H3K4 methylation as a mark of active transcription, enhancer signatures, and developmentally poised genes is discussed. The misregulation of histone H2B monoubiquitination and H3K4 methylation result in the pathogenesis of human diseases, including cancer. Recent findings in this regard are also examined.

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Crossref · 10.1146/annurev-biochem-051710-134100

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  • SET domain-containing histone methyltransferases such as Trithorax/MLL1/2-COMPASS and PRC2 methylate lysine residues in the histone H3 amino-terminal tail and are essential for normal development.

    “The SET domain-containing histone methyltransferases such as Trithorax/MLL1/2-COMPASS and Polycomb Repressive Complex 2 (PRC2) methylate lysine residues in the histone H3 amino-terminal tail and are essential for normal development [1].”

    From Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling (2014) · cites this paper as [1]

    The Introduction identifies trithorax and Polycomb proteins as SET-domain-containing methyltransferases involved in homeotic gene regulation. Sections 3.4 and 3.6 describe MLL1/MLL2-mediated H3K4 methylation, Polycomb-group H3K27 methylation, and embryonic lethality after MLL1 deletion. The copy does not specifically establish that PRC2 itself is essential for normal development. (LLM, conf=0.82)

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Research works printed but not linked: 7

  1. [29]Smith E Shilatifard A 2010 The chromatin signaling pathway: diverse mechanisms of recruitment of histone-modifying enzymes and varied biological outcomes Molecular cell 40 689 701 21145479 PMC3037032
  2. [66]Wu M Wang PF Lee JS Martin-Brown S Florens L 2008 Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS Molecular and cellular biology 28 7337 44 18838538 PMC2593441
  3. [72]Lee JH Tate CM You JS Skalnik DG 2007 Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex The Journal of biological chemistry 282 13419 28 17355966
  4. [74]Eissenberg JC Shilatifard A 2010 Histone H3 lysine 4 (H3K4) methylation in development and differentiation Dev Biol 339 240 9 19703438 PMC3711867
  5. [80]Lee JH Skalnik DG 2008 Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A Histone H3-Lys4 methyltransferase complex to transcription start sites of transcribed human genes Molecular and cellular biology 28 609 18 17998332 PMC2223426
  6. [162]Mohan M Lin C Guest E Shilatifard A 2010 Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis Nat Rev Cancer 10 721 8 20844554
  7. [197]Daniel JA Santos MA Wang Z Zang C Schwab KR PTIP promotes chromatin changes critical for immunoglobulin class switch recombination Science 329 917 23 20671152 PMC3008398

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Authors
Shilatifard, A.
Affiliations
Stowers Institute for Medical Research (US)
Corresponding author
Shilatifard, Ali
Venue
Annual Review of Biochemistry
Published
2012-07-07
Volume
81
Issue
1
Pages
65-95
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
OpenAlex
W2121910267
Cited by
1,091
References
197
Citations by year
2026: 47 · 2025: 67 · 2024: 91 · 2023: 88 · 2022: 81 · 2021: 91 · 2020: 89 · 2019: 99 · 2018: 75 · 2017: 71 · 2016: 79 · 2015: 80 · 2014: 78 · 2013: 45 · 2012: 10
FWCI
6.21
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA150265, R01CA089455, R01CA89455)
  • National Institute of General Medical Sciences (R01GM069905)
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
compass, histone H3 lysine 4 methylation, histone H2B monoubiquitination, cancer, epigenetic regulation, Saccharomyces cerevisiae, Drosophila
MeSH terms
Histone Methyltransferases, Animals, DNA Repair, Gene Expression Regulation, Humans, Neoplasms, Histone-Lysine N-Methyltransferase, Transcription, Genetic

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