Chromatin and epigenetic landscape of the human brain important for obesity

Radu Zabet (primary)
Blizard Institute
Queen Mary University of London
Dr Elena Bochukova (secondary)
Blizard Institute
Queen Mary University of London

Abstract

Established very early in human development, body weight regulation is brain-governed by the hypothalamus. Consequently, hypothalamic dysfunction leads to obesity, and therefore understanding of gene regulatory logic in this brain area is of high importance. Cellular identity is provided by the set of genes that are active, which are controlled by the epigenetic landscape of the non-coding genome. Here, we plan to reconstruct the genome wide profiles of several architectural proteins and epigenetic marks in the hypothalamus. We will use then these datasets to identify and characterise the non-coding regulatory regions of the genome that control gene activity in hypothalamus.


References

Bochukova et al (2010) Large, rare chromosomal deletions associated with severe early-onset obesity Nature. 463(7281):666-70
Bochukova et al (2018) A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome Cell Rep. 22(13):3401-3408
Chathoth KT & Zabet NR (2019) Chromatin architecture reorganization during neuronal cell differentiation in Drosophila genome Genome Res 29:613
Beagan JA et al (2017) YY1 and CTCF orchestrate a 3D chromatin looping switch during neural lineage commitment Genome Res 27:1
Oh et al (2021) Enhancer release and retargeting activates disease-susceptibility genes Nature https://doi.org/10.1038/s41586-021-03577-1


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
GeneticsNeurobiology
Techniques & Approaches
BioinformaticsMathematics / StatisticsMolecular Biology