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Publication : Dual Chromatin and Cytoskeletal Remodeling by SETD2.

First Author  Park IY Year  2016
Journal  Cell Volume  166
Issue  4 Pages  950-962
PubMed ID  27518565 Mgi Jnum  J:236080
Mgi Id  MGI:5804701 Doi  10.1016/j.cell.2016.07.005
Citation  Park IY, et al. (2016) Dual Chromatin and Cytoskeletal Remodeling by SETD2. Cell 166(4):950-62
abstractText  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 alpha-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.
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