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.

Trichostatin A decreases the levels of MeCP2 expression and phosphorylation and increases its chromatin binding affinity / G. Katrina V., M.D.P. Alexia, T. Monica, C. Manjinder S., T. Anita A., G. Taylor L., S. Gilda, C. Robert L., K. Oliver, H. Michael, M. Kristal, U. Alan, N. Landsberger, A. Juan. - In: EPIGENETICS. - ISSN 1559-2294. - 12:11(2017), pp. 934-944. [10.1080/15592294.2017.1380760]

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

N. Landsberger
Penultimo
;
2017

Abstract

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.
English
MeCP2; Trichostatin A (TSA); chromatin; histone acetylation; miR-132
Settore BIO/11 - Biologia Molecolare
Articolo
Esperti anonimi
Ricerca di base
Pubblicazione scientifica
2017
Taylor and Francis Inc.
12
11
934
944
11
Pubblicato
Periodico con rilevanza internazionale
scopus
pubmed
crossref
Aderisco
info:eu-repo/semantics/article
Trichostatin A decreases the levels of MeCP2 expression and phosphorylation and increases its chromatin binding affinity / G. Katrina V., M.D.P. Alexia, T. Monica, C. Manjinder S., T. Anita A., G. Taylor L., S. Gilda, C. Robert L., K. Oliver, H. Michael, M. Kristal, U. Alan, N. Landsberger, A. Juan. - In: EPIGENETICS. - ISSN 1559-2294. - 12:11(2017), pp. 934-944. [10.1080/15592294.2017.1380760]
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G. Katrina V., M.D.P. Alexia, T. Monica, C. Manjinder S., T. Anita A., G. Taylor L., S. Gilda, C. Robert L., K. Oliver, H. Michael, M. Kristal, U. Ala...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/545248
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