Metabolic Regulation of CTCF Expression and Chromatin Association Dictates Starvation Response in Mice and Flies

Overview

Journal iScience

Publisher Cell Press

Date 2023 Jul 7

PMID 37416476

Authors

Devashish Sen

Babukrishna Maniyadath

Shreyam Chowdhury

Arshdeep Kaur

Subhash Khatri

Arnab Chakraborty

Neelay Mehendale

Snigdha Nadagouda

U S Sandra

Siddhesh S Kamat

Ullas Kolthur-Seetharam

Affiliations

Soon will be listed here.

Abstract

Coordinated temporal control of gene expression is essential for physiological homeostasis, especially during metabolic transitions. However, the interplay between chromatin architectural proteins and metabolism in regulating transcription is less understood. Here, we demonstrate a conserved bidirectional interplay between CTCF (CCCTC-binding factor) expression/function and metabolic inputs during feed-fast cycles. Our results indicate that its loci-specific functional diversity is associated with physiological plasticity in mouse hepatocytes. CTCF differential expression and long non-coding RNA-Jpx mediated changes in chromatin occupancy, unraveled its paradoxical yet tuneable functions, which are governed by metabolic inputs. We illustrate the key role of CTCF in controlling temporal cascade of transcriptional response, with effects on hepatic mitochondrial energetics and lipidome. Underscoring the evolutionary conservation of CTCF-dependent metabolic homeostasis, CTCF knockdown in flies abrogated starvation resistance. In summary, we demonstrate the interplay between CTCF and metabolic inputs that highlights the coupled plasticity of physiological responses and chromatin function.

Citing Articles

Identification of ABHD6 as a lysophosphatidylserine lipase in the mammalian liver and kidneys.

Chakraborty A, Punnamraju P, Sajeevan T, Kaur A, Kolthur-Seetharam U, Kamat S J Biol Chem. 2025; 301(2):108157.

PMID: 39761854 PMC: 11808726. DOI: 10.1016/j.jbc.2025.108157.

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