Dual Chromatin and Cytoskeletal Remodeling by SETD2

In Young Park, Reid T. Powell, Durga Nand Tripathi, Ruhee Dere, Thai H. Ho, T. Lynne Blasius, Yun Chen Chiang, Ian J. Davis, Catherine C. Fahey, Kathryn E. Hacker, Kristen J. Verhey, Mark T. Bedford, Eric Jonasch, W. Kimryn Rathmell, Cheryl Lyn Walker

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Posttranslational modifications (PTMs) of tubulin specify microtubules for specialized cellular functions and comprise what is termed a “tubulin code.” PTMs of histones comprise an analogous “histone code,” although the “readers, writers, and erasers” of the cytoskeleton and epigenome have heretofore been distinct. We show that methylation is a PTM of dynamic microtubules and that the histone methyltransferase SET-domain-containing 2 (SETD2), which is responsible for H3 lysine 36 trimethylation (H3K36me3) of histones, also methylates α-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy. These data now identify SETD2 as a dual-function methyltransferase for both chromatin and the cytoskeleton and show a requirement for methylation in maintenance of genomic stability and the integrity of both the tubulin and histone codes.

Original languageEnglish (US)
Pages (from-to)950-962
Number of pages13
Issue number4
StatePublished - Aug 11 2016

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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