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Transitions in chromatin conformation shaped by fatty acids and the circadian clock underlie hepatic transcriptional reorganization in obese mice.
Pacheco-Bernal, Ignacio; Becerril-Pérez, Fernando; Bustamante-Zepeda, Marcia; González-Suárez, Mirna; Olmedo-Suárez, Miguel A; Hernández-Barrientos, Luis Ricardo; Alarcón-Del-Carmen, Alejandro; Escalante-Covarrubias, Quetzalcoatl; Mendoza-Viveros, Lucía; Hernández-Lemus, Enrique; León-Del-Río, Alfonso; de la Rosa-Velázquez, Inti A; Orozco-Solis, Ricardo; Aguilar-Arnal, Lorena.
Afiliação
  • Pacheco-Bernal I; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • Becerril-Pérez F; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • Bustamante-Zepeda M; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • González-Suárez M; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • Olmedo-Suárez MA; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • Hernández-Barrientos LR; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • Alarcón-Del-Carmen A; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • Escalante-Covarrubias Q; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • Mendoza-Viveros L; Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • Hernández-Lemus E; Laboratorio de Cronobiología, Metabolismo y Envejecimiento, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
  • León-Del-Río A; Centro de Investigacíon sobre el Envejecimiento, Centro de Investigación y de Estudios Avanzados (CIE-CINVESTAV), Mexico City, México.
  • de la Rosa-Velázquez IA; Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, Mexico.
  • Orozco-Solis R; Department of Computational Genomics, Centro de Ciencias de La Complejidad (C3), Instituto Nacional de Medicina Genómica (INMEGEN), Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Aguilar-Arnal L; Departamento de Medicina Genómica y Toxicología Ambiental, Programa Institucional de Cáncer de Mama, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
Cell Mol Life Sci ; 81(1): 309, 2024 Jul 26.
Article em En | MEDLINE | ID: mdl-39060446
ABSTRACT
The circadian clock system coordinates metabolic, physiological, and behavioral functions across a 24-h cycle, crucial for adapting to environmental changes. Disruptions in circadian rhythms contribute to major metabolic pathologies like obesity and Type 2 diabetes. Understanding the regulatory mechanisms governing circadian control is vital for identifying therapeutic targets. It is well characterized that chromatin remodeling and 3D structure at genome regulatory elements contributes to circadian transcriptional cycles; yet the impact of rhythmic chromatin topology in metabolic disease is largely unexplored. In this study, we explore how the spatial configuration of the genome adapts to diet, rewiring circadian transcription and contributing to dysfunctional metabolism. We describe daily fluctuations in chromatin contacts between distal regulatory elements of metabolic control genes in livers from lean and obese mice and identify specific lipid-responsive regions recruiting the clock molecular machinery. Interestingly, under high-fat feeding, a distinct interactome for the clock-controlled gene Dbp strategically promotes the expression of distal metabolic genes including Fgf21. Alongside, new chromatin loops between regulatory elements from genes involved in lipid metabolism control contribute to their transcriptional activation. These enhancers are responsive to lipids through CEBPß, counteracting the circadian repressor REVERBa. Our findings highlight the intricate coupling of circadian gene expression to a dynamic nuclear environment under high-fat feeding, supporting a temporally regulated program of gene expression and transcriptional adaptation to diet.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Ácidos Graxos / Relógios Circadianos / Fígado / Camundongos Endogâmicos C57BL / Camundongos Obesos / Obesidade Limite: Animals Idioma: En Revista: Cell Mol Life Sci Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Ácidos Graxos / Relógios Circadianos / Fígado / Camundongos Endogâmicos C57BL / Camundongos Obesos / Obesidade Limite: Animals Idioma: En Revista: Cell Mol Life Sci Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Suíça