Sex-specific Epigenetic Development in the Mouse Hypothalamic Arcuate Nucleus Pinpoints Human Genomic Regions Associated with Body Mass Index

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Sep 28

PMID 36170368

Authors

Harry MacKay

Chathura J Gunasekara

Kit-Yi Yam

Dollada Srisai

Hari Krishna Yalamanchili

Yumei Li

Rui Chen

Cristian Coarfa

Robert A Waterland

Affiliations

Soon will be listed here.

Abstract

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and occurs in genomic regions enriched for heritability of body mass index in humans. Our results offer a potential explanation for both the limited ontogenic windows for and sex differences in sensitivity to developmental programming of obesity and provide a rich resource for epigenetic analyses of developmental programming of energy balance.

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