title: Dual Chromatin and Cytoskeletal Remodeling by SETD2.
abstract: 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.
authors: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors: In Young
authors: IY
authors: Park
authors: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors: Reid T
authors: RT
authors: Powell
authors: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors: Durga Nand
authors: DN
authors: Tripathi
authors: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors: Ruhee
authors: R
authors: Dere
authors: Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
authors: Thai H
authors: TH
authors: Ho
authors: Department of Cell and Developmental Biology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
authors: T Lynne
authors: TL
authors: Blasius
authors: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: Yun-Chen
authors: YC
authors: Chiang
authors: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: Ian J
authors: IJ
authors: Davis
authors: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: Catherine C
authors: CC
authors: Fahey
authors: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: Kathryn E
authors: KE
authors: Hacker
authors: Department of Cell and Developmental Biology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Kristen J
authors: KJ
authors: Verhey
authors: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors: Mark T
authors: MT
authors: Bedford
authors: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Eric
authors: E
authors: Jonasch
authors: Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA.
authors: W Kimryn
authors: WK
authors: Rathmell
authors: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA. Electronic address: cherylw@bcm.edu.
authors: Cheryl Lyn
authors: CL
authors: Walker
mesh_terms: D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D048749:Cytokinesis; D003599:Cytoskeleton / Q000378:metabolism*; D042822:Genomic Instability; D042421:Histone Code; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D011499:Protein Processing, Post-Translational; D014404:Tubulin / Q000378:metabolism
chemical_list: D006657:Histones; D014404:Tubulin; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human; D008239:Lysine