RRC ID 12774
Author Aoyama K, Fukumoto Y, Ishibashi K, Kubota S, Morinaga T, Horiike Y, Yuki R, Takahashi A, Nakayama Y, Yamaguchi N.
Title Nuclear c-Abl-mediated tyrosine phosphorylation induces chromatin structural changes through histone modifications that include H4K16 hypoacetylation.
Journal Exp. Cell Res.
Abstract c-Abl tyrosine kinase, which is ubiquitously expressed, has three nuclear localization signals and one nuclear export signal and can shuttle between the nucleus and the cytoplasm. c-Abl plays important roles in cell proliferation, adhesion, migration, and apoptosis. Recently, we developed a pixel imaging method for quantitating the level of chromatin structural changes and showed that nuclear Src-family tyrosine kinases are involved in chromatin structural changes upon growth factor stimulation. Using this method, we show here that nuclear c-Abl induces chromatin structural changes in a manner dependent on the tyrosine kinase activity. Expression of nuclear-targeted c-Abl drastically increases the levels of chromatin structural changes, compared with that of c-Abl. Intriguingly, nuclear-targeted c-Abl induces heterochromatic profiles of histone methylation and acetylation, including hypoacetylation of histone H4 acetylated on lysine 16 (H4K16Ac). The level of heterochromatic histone modifications correlates with that of chromatin structural changes. Adriamycin-induced DNA damage stimulates translocation of c-Abl into the nucleus and induces chromatin structural changes together with H4K16 hypoacetylation. Treatment with trichostatin A, a histone deacetylase inhibitor, blocks chromatin structural changes but not nuclear tyrosine phosphorylation by c-Abl. These results suggest that nuclear c-Abl plays an important role in chromatin dynamics through nuclear tyrosine phosphorylation-induced heterochromatic histone modifications.
Volume 317(20)
Pages 2874-903
Published 2011-12-10
DOI 10.1016/j.yexcr.2011.09.013
PII S0014-4827(11)00383-1
PMID 22001646
MeSH Acetylation Chromatin / drug effects Chromatin / metabolism* HeLa Cells Histone Deacetylase Inhibitors / pharmacology Histones / metabolism* Humans Hydroxamic Acids / pharmacology Methylation Phosphorylation Proto-Oncogene Proteins c-abl / metabolism* Tumor Cells, Cultured Tyrosine / metabolism* src-Family Kinases / metabolism
IF 3.309
Times Cited 17
DNA material pENTR4-H1 (RDB04395)