Sex-based Mhrt Methylation chromatinizes MeCP2 in the heart

Harikrishnan, K. N., Okabe, J., Mathiyalagan, P., Khan, A. W., Jadaan, S. A., Sarila, G., Ziemann, M., Khurana, I., Maxwell, S.S ., Du, X. J. and El-Osta, A. 2019, Sex-based Mhrt Methylation chromatinizes MeCP2 in the heart, iScience, vol. 17, pp. 288-301, doi: 10.1016/j.isci.2019.06.031.

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Title Sex-based Mhrt Methylation chromatinizes MeCP2 in the heart
Author(s) Harikrishnan, K. N.
Okabe, J.
Mathiyalagan, P.
Khan, A. W.
Jadaan, S. A.
Sarila, G.
Ziemann, M.ORCID iD for Ziemann, M.
Khurana, I.
Maxwell, S.S .
Du, X. J.
El-Osta, A.
Journal name iScience
Volume number 17
Start page 288
End page 301
Total pages 33
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2019-07-26
ISSN 2589-0042
Summary © 2019 The Author(s) In the heart, primary microRNA-208b (pri-miR-208b) and Myheart (Mhrt) are long non-coding RNAs (lncRNAs) encoded by the cardiac myosin heavy chain genes. Although preclinical studies have shown that lncRNAs regulate gene expression and are protective for pathological hypertrophy, the mechanism underlying sex-based differences remains poorly understood. In this study, we examined DNA- and RNA-methylation-dependent regulation of pri-miR-208b and Mhrt. Expression of pri-miR-208b is elevated in the left ventricle of the female heart. Despite indistinguishable DNA methylation between sexes, the interaction of MeCP2 on chromatin is subject to RNase digestion, highlighting that affinity of the methyl-CG reader is broader than previously thought. A specialized procedure to isolate RNA from soluble cardiac chromatin emphasizes sex-based affinity of an MeCP2 co-repressor complex with Rest and Hdac2. Sex-specific Mhrt methylation chromatinizes MeCP2 at the pri-miR-208b promoter and extends the functional relevance of default transcriptional suppression in the heart.
Language eng
DOI 10.1016/j.isci.2019.06.031
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HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2019, The Authors
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