Histone Post-translational Modifications - Cause and Consequence of Genome Function

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2022 Mar 26

PMID 35338361

Authors

Gonzalo Millan-Zambrano

Adam Burton

Andrew J Bannister

Robert Schneider

Affiliations

Soon will be listed here.

Abstract

Much has been learned since the early 1960s about histone post-translational modifications (PTMs) and how they affect DNA-templated processes at the molecular level. This understanding has been bolstered in the past decade by the identification of new types of histone PTM, the advent of new genome-wide mapping approaches and methods to deposit or remove PTMs in a locally and temporally controlled manner. Now, with the availability of vast amounts of data across various biological systems, the functional role of PTMs in important processes (such as transcription, recombination, replication, DNA repair and the modulation of genomic architecture) is slowly emerging. This Review explores the contribution of histone PTMs to the regulation of genome function by discussing when these modifications play a causative (or instructive) role in DNA-templated processes and when they are deposited as a consequence of such processes, to reinforce and record the event. Important advances in the field showing that histone PTMs can exert both direct and indirect effects on genome function are also presented.

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References

Luger K, Dechassa M, Tremethick D . New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?. Nat Rev Mol Cell Biol. 2012; 13(7):436-47. PMC: 3408961. DOI: 10.1038/nrm3382. View

Lai W, Pugh B . Understanding nucleosome dynamics and their links to gene expression and DNA replication. Nat Rev Mol Cell Biol. 2017; 18(9):548-562. PMC: 5831138. DOI: 10.1038/nrm.2017.47. View

Turner B . Decoding the nucleosome. Cell. 1993; 75(1):5-8. View

Dai Z, Ramesh V, Locasale J . The evolving metabolic landscape of chromatin biology and epigenetics. Nat Rev Genet. 2020; 21(12):737-753. PMC: 8059378. DOI: 10.1038/s41576-020-0270-8. View

Wiese M, Bannister A . Two genomes, one cell: Mitochondrial-nuclear coordination via epigenetic pathways. Mol Metab. 2020; 38:100942. PMC: 7300384. DOI: 10.1016/j.molmet.2020.01.006. View

Martire S, Banaszynski L . The roles of histone variants in fine-tuning chromatin organization and function. Nat Rev Mol Cell Biol. 2020; 21(9):522-541. PMC: 8245300. DOI: 10.1038/s41580-020-0262-8. View

Nacev B, Feng L, Bagert J, Lemiesz A, Gao J, Soshnev A . The expanding landscape of 'oncohistone' mutations in human cancers. Nature. 2019; 567(7749):473-478. PMC: 6512987. DOI: 10.1038/s41586-019-1038-1. View

BYVOET P, SHEPHERD G, Hardin J, NOLAND B . The distribution and turnover of labeled methyl groups in histone fractions of cultured mammalian cells. Arch Biochem Biophys. 1972; 148(2):558-67. DOI: 10.1016/0003-9861(72)90174-9. View

Lieberman-Aiden E, van Berkum N, Williams L, Imakaev M, Ragoczy T, Telling A . Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009; 326(5950):289-93. PMC: 2858594. DOI: 10.1126/science.1181369. View

10.

Dixon J, Selvaraj S, Yue F, Kim A, Li Y, Shen Y . Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012; 485(7398):376-80. PMC: 3356448. DOI: 10.1038/nature11082. View

11.

Allfrey V, Faulkner R, Mirsky A . ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS. Proc Natl Acad Sci U S A. 1964; 51:786-94. PMC: 300163. DOI: 10.1073/pnas.51.5.786. View

12.

Shogren-Knaak M, Ishii H, Sun J, Pazin M, Davie J, Peterson C . Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science. 2006; 311(5762):844-7. DOI: 10.1126/science.1124000. View

13.

Cosgrove M, Boeke J, Wolberger C . Regulated nucleosome mobility and the histone code. Nat Struct Mol Biol. 2004; 11(11):1037-43. DOI: 10.1038/nsmb851. View

14.

Neumann H, Hancock S, Buning R, Routh A, Chapman L, Somers J . A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol Cell. 2009; 36(1):153-63. PMC: 2856916. DOI: 10.1016/j.molcel.2009.07.027. View

15.

Verdin E, Ott M . 50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond. Nat Rev Mol Cell Biol. 2015; 16(4):258-64. DOI: 10.1038/nrm3931. View

16.

Durrin L, MANN R, Kayne P, Grunstein M . Yeast histone H4 N-terminal sequence is required for promoter activation in vivo. Cell. 1991; 65(6):1023-31. DOI: 10.1016/0092-8674(91)90554-c. View

17.

Protacio R, Li G, Lowary P, Widom J . Effects of histone tail domains on the rate of transcriptional elongation through a nucleosome. Mol Cell Biol. 2000; 20(23):8866-78. PMC: 86542. DOI: 10.1128/MCB.20.23.8866-8878.2000. View

18.

Zhang W, BONE J, Edmondson D, Turner B, Roth S . Essential and redundant functions of histone acetylation revealed by mutation of target lysines and loss of the Gcn5p acetyltransferase. EMBO J. 1998; 17(11):3155-67. PMC: 1170654. DOI: 10.1093/emboj/17.11.3155. View

19.

Nitsch S, Shahidian L, Schneider R . Histone acylations and chromatin dynamics: concepts, challenges, and links to metabolism. EMBO Rep. 2021; 22(7):e52774. PMC: 8406397. DOI: 10.15252/embr.202152774. View

20.

Tan M, Luo H, Lee S, Jin F, Yang J, Montellier E . Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011; 146(6):1016-28. PMC: 3176443. DOI: 10.1016/j.cell.2011.08.008. View