Trichostatin A decreases the levels of MeCP2 expression and phosphorylation and increases its chromatin binding affinity.

Autor:	Good KV; a Department of Biochemistry and Microbiology , University of Victoria , Victoria , BC , V8W 3P6 , Canada., Martínez de Paz A; a Department of Biochemistry and Microbiology , University of Victoria , Victoria , BC , V8W 3P6 , Canada., Tyagi M; a Department of Biochemistry and Microbiology , University of Victoria , Victoria , BC , V8W 3P6 , Canada., Cheema MS; a Department of Biochemistry and Microbiology , University of Victoria , Victoria , BC , V8W 3P6 , Canada., Thambirajah AA; a Department of Biochemistry and Microbiology , University of Victoria , Victoria , BC , V8W 3P6 , Canada.; b Douglas Hospital Research Center , Department of Psychiatry , McGill University , Montréal , Québec H3G 1Y6 , Canada., Gretzinger TL; a Department of Biochemistry and Microbiology , University of Victoria , Victoria , BC , V8W 3P6 , Canada., Stefanelli G; c Department of Medical Biotechnology and Translational Medicine , University of Milan , Milan , Italy., Chow RL; d Department of Biology , University of Victoria , Victoria , BC , V8W 3P6 , Canada., Krupke O; d Department of Biology , University of Victoria , Victoria , BC , V8W 3P6 , Canada., Hendzel M; e Department of Cell Biology , Faculty of Medicine and Dentistry , University of Alberta , Edmonton , Alberta , Canada.; f Department of Oncology and Department of Cell Biology , Faculty of Medicine and Dentistry , University of Alberta , Edmonton , Alberta , Canada., Missiaen K; f Department of Oncology and Department of Cell Biology , Faculty of Medicine and Dentistry , University of Alberta , Edmonton , Alberta , Canada., Underhill A; f Department of Oncology and Department of Cell Biology , Faculty of Medicine and Dentistry , University of Alberta , Edmonton , Alberta , Canada., Landsberger N; c Department of Medical Biotechnology and Translational Medicine , University of Milan , Milan , Italy., Ausió J; a Department of Biochemistry and Microbiology , University of Victoria , Victoria , BC , V8W 3P6 , Canada.
Jazyk:	angličtina
Zdroj:	Epigenetics [Epigenetics] 2017; Vol. 12 (11), pp. 934-944. Date of Electronic Publication: 2017 Dec 05.
DOI:	10.1080/15592294.2017.1380760
Abstrakt:	MeCP2 binds to methylated DNA in a chromatin context and has an important role in cancer and brain development and function. Histone deacetylase (HDAC) inhibitors are currently being used to palliate many cancer and neurological disorders. Yet, the molecular mechanisms involved are not well known for the most part and, in particular, the relationship between histone acetylation and MeCP2 is not well understood. In this paper, we study the effect of the HDAC inhibitor trichostatin A (TSA) on MeCP2, a protein whose dysregulation plays an important role in these diseases. We find that treatment of cells with TSA decreases the phosphorylation state of this protein and appears to result in a higher MeCP2 chromatin binding affinity. Yet, the binding dynamics with which the protein binds to DNA appear not to be significantly affected despite the chromatin reorganization resulting from the high levels of acetylation. HDAC inhibition also results in an overall decrease in MeCP2 levels of different cell lines. Moreover, we show that miR132 increases upon TSA treatment, and is one of the players involved in the observed downregulation of MeCP2.
Databáze:	MEDLINE
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