Dual Chromatin and Cytoskeletal Remodeling by SETD2. Academic Article uri icon


  • 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 thecytoskeleton and epigenome have heretofore been distinct. We show that methylation is a PTM ofdynamic microtubules and that the histone methyltransferase SET-domain-containing 2 (SETD2), which is responsible for H3 lysine 36 trimethylation (H3K36me3) of histones, also methylates -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.

published proceedings

  • Cell

altmetric score

  • 17.75

author list (cited authors)

  • Park, I. Y., Powell, R. T., Tripathi, D. N., Dere, R., Ho, T. H., Blasius, T. L., ... Walker, C. L.

citation count

  • 170

complete list of authors

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

publication date

  • August 2016

published in