Phosphorylation of histones by tissue transglutaminase.
Tissue transglutaminase 2 (TG2) has recently been shown to have intrinsic serine/threonine kinase activity. Since histones are known to be cross-linked by TG2, we investigated whether histones are also substrates for TG2 kinase activity. TG2 was able to phosphorylate H1, H2A, H2B, H3, and H4 histones in vitro. Using peptide substrates and phosphospecific antibodies we demonstrated that TG2 phosphorylated Ser(10) in H3 and that this phosphorylation was reduced by acetylation, whereas phosphorylation of Ser(10) by TG2 enhanced acetylation. Furthermore we demonstrated that exogenous TG2 phosphorylated H1 and H3 in nucleosome preparations. We examined the abundance of TG2 in DNA-associated proteins from MCF-7 cells treated with phorbol ester (TPA) and 17beta-estradiol (E2). TG2 abundance was significantly reduced in E2-treated cells and enhanced in TPA-treated cells. In summary we have demonstrated that TG2 is able to phosphorylate purified histone proteins, and H3 and H1 in chromatin preparations, and it is associated with chromatin in breast cancer cells. These studies suggest a novel role for TG2 in the regulation of chromatin structure and function.
Mishra
Suresh
S
Department of Physiology, University of Manitoba, Winnipeg, Manitoba R3E 0W3, Canada.
Saleh
Ali
A
Espino
Paula S
PS
Davie
James R
JR
Murphy
Liam J
LJ
D000107:Acetylation; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D019204:GTP-Binding Proteins; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012694:Serine / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
D006657:Histones; D009707:Nucleosomes; D010455:Peptides; D010710:Phosphates; C000717608:TGM2 protein, human; D012694:Serine; D051548:Histone Acetyltransferases; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins