Dual Chromatin and Cytoskeletal Remodeling by SETD2

被引：185

作者：

Park, In Young ^{[1
,10
]}

Powell, Reid T. ^{[1
,10
]}

Tripathi, Durga Nand ^{[1
,10
]}

Dere, Ruhee ^{[1
,10
]}

Ho, Thai H. ^{[2
]}

Blasius, T. Lynne ^{[3
]}

Chiang, Yun-Chen ^{[4
,5
]}

Davis, Ian J. ^{[4
,5
,6
]}

Fahey, Catherine C. ^{[4
,5
]}

Hacker, Kathryn E. ^{[4
,5
]}

Verhey, Kristen J. ^{[3
]}

Bedford, Mark T. ^{[7
]}

Jonasch, Eric ^{[8
]}

Rathmell, W. Kimryn ^{[4
,5
,9
]}

Walker, Cheryl Lyn ^{[1
,10
]}

机构：

[1] Texas A&M Hlth Sci Ctr, Inst Biosci & Technol, Ctr Translat Canc Res, Houston, TX 77030 USA

[2] Mayo Clin Arizona, Div Hematol Oncol, Scottsdale, AZ 85259 USA

[3] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA

[4] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Smithville, TX 78957 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[9] Vanderbilt Univ, Div Hematol Oncol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA

[10] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA

来源：

CELL | 2016年 / 166卷 / 04期

关键词：

RENAL-CELL CARCINOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HISTONE H3K36 METHYLATION; RNA-POLYMERASE-II; EPIGENETIC REGULATORS; POSTTRANSLATIONAL MODIFICATIONS; HOMOLOGOUS RECOMBINATION; BRANCHED EVOLUTION; CANCER GENOMICS; TUBULIN CODE;

D O I：

10.1016/j.cell.2016.07.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 a-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.

引用

页码：950 / 962

页数：13

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