Unique and Shared Roles for Histone H3K36 Methylation States in Transcription Regulation Functions

Julia V DiFiore; Travis S Ptacek; Yi Wang; Bing Li; Jeremy M Simon; Brian D Strahl

doi:10.1016/j.celrep.2020.107751

Unique and Shared Roles for Histone H3K36 Methylation States in Transcription Regulation Functions

Cell Rep. 2020 Jun 9;31(10):107751. doi: 10.1016/j.celrep.2020.107751.

Authors

Julia V DiFiore¹, Travis S Ptacek², Yi Wang³, Bing Li⁴, Jeremy M Simon⁵, Brian D Strahl⁶

Affiliations

¹ Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
² UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
³ Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China.
⁴ Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁵ UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
⁶ Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: brian_strahl@med.unc.edu.

Abstract

Set2 co-transcriptionally methylates lysine 36 of histone H3 (H3K36), producing mono-, di-, and trimethylation (H3K36me1/2/3). These modifications recruit or repel chromatin effector proteins important for transcriptional fidelity, mRNA splicing, and DNA repair. However, it was not known whether the different methylation states of H3K36 have distinct biological functions. Here, we use engineered forms of Set2 that produce different lysine methylation states to identify unique and shared functions for H3K36 modifications. Although H3K36me1/2 and H3K36me3 are functionally redundant in many SET2 deletion phenotypes, we found that H3K36me3 has a unique function related to Bur1 kinase activity and FACT (facilitates chromatin transcription) complex function. Further, during nutrient stress, either H3K36me1/2 or H3K36me3 represses high levels of histone acetylation and cryptic transcription that arises from within genes. Our findings uncover the potential for the regulation of diverse chromatin functions by different H3K36 methylation states.

Keywords: H3K36 methylation; RNA Polymerase II; Set2; chromatin; cryptic transcription; epigenetics; histone; nutrient stress; transcriptional regulation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Histones / metabolism*
Humans
Methylation
Protein Processing, Post-Translational / genetics*
Transcription, Genetic / genetics*

Substances

Histones

Abstract

Publication types

MeSH terms

Substances

Grants and funding