Metabolic regulation of CTCF expression and chromatin association dictates starvation response in mice and flies.
iScience
; 26(7): 107128, 2023 Jul 21.
Article
in En
| MEDLINE
| ID: mdl-37416476
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Risk_factors_studies
Language:
En
Journal:
IScience
Year:
2023
Document type:
Article
Affiliation country: