Mechanisms involved in epigenetic down-regulation of Gfap under maternal hypothyroidism

Biochemical and Biophysical Research Communications
Praveen KumarRohit A Sinha

Abstract

Thyroid hormones (TH) of maternal origin are crucial regulator of mammalian brain development during embryonic period. Although maternal TH deficiency during the critical periods of embryonic neo-cortical development often results in irreversible clinical outcomes, the fundamental basis of these abnormalities at a molecular level is still obscure. One of the key developmental process affected by maternal TH insufficiency is the delay in astrocyte maturation. Glial fibrillary acidic protein (Gfap) is a predominant cell marker of mature astrocyte and is regulated by TH status. Inspite, of being a TH responsive gene during neocortical development the mechanistic basis of Gfap transcriptional regulation by TH has remained elusive. In this study using rat model of maternal hypothyroidism, we provide evidence for an epigenetic silencing of Gfap under TH insufficiency and its recovery upon TH supplementation. Our results demonstrate increased DNA methylation coupled with decreased histone acetylation at the Gfap promoter leading to suppression of Gfap expression under maternal hypothyroidism. In concordance, we also observed a significant increase in histone deacetylase (HDAC) activity in neocortex of TH deficient embryos. Collectivel...Continue Reading

Citations

Jul 1, 2020·Thyroid : Official Journal of the American Thyroid Association·Meng RaoShuhua Zhao
Jan 10, 2021·Molecular and Cellular Endocrinology·Juliane de Souza CardosoRejane Giacomelli Tavares
Mar 11, 2020·Experimental and Molecular Pathology·Aditya UpadhyayMadan M Godbole
Feb 27, 2021·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Omyma G AhmedNessren M Abd El-Rady

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