ArticleCell biology and toxicology2022
Cooperation of ATF4 and CTCF promotes adipogenesis through transcriptional regulation.
Article in Cell biology and toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 27 citations in OpenAlex.
- C/EBPδ as a Regulatory Node in Adipocytes: Roles in Differentiation, Metabolism, and Immune Function.Biomolecules · 2026Review
- HERP constrains white adipose expansion and inflammation by STEAP4 stabilization.Cell death and differentiation · 2026Article
- Obesity disrupts ILC2 metabolic and functional homeostasis by inhibiting mTORC1 signaling.Cellular & molecular immunology · 2026Article
- The ATF4-glutamine axis: a central node in cancer metabolism, stress adaptation, and therapeutic targeting.Cell death discovery · 2025Review
- Molecular mechanism of nano-vitamin A-mediated regulation of intramuscular fat deposition involving noncoding RNAs in pigs.BMC genomics · 2025Article
- White Adipocyte Stem Cell Expansion Through Infant Formula Feeding: New Insights into Epigenetic Programming Explaining the Early Protein Hypothesis of Obesity.International journal of molecular sciences · 2025Review
- Basic biology and roles of CEBPD in cardiovascular disease.Cell death discovery · 2025Review
- Systematic functional characterization of non-coding regulatory SNPs associated with central obesity.American journal of human genetics · 2025Article
- Integration of ATAC-Seq and RNA-Seq Reveals VDR-SELENBP1 Axis Promotes Adipogenesis of Porcine Intramuscular Preadipocytes.International journal of molecular sciences · 2024Article
- Risk of Fat Mass- and Obesity-Associated Gene-Dependent Obesogenic Programming by Formula Feeding Compared to Breastfeeding.Nutrients · 2024Review
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
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- Article
- Control of murine brown adipocyte development by GATA6.Developmental cell · 2023Article
- A single nuclei atlas of aging human abdominal subcutaneous white adipose tissue.Research square · 2023Article
- A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response.Frontiers in molecular neuroscience · 2023Review
- Dynamics of transcriptome and chromatin accessibility revealed sequential regulation of potential transcription factors during the brown adipose tissue whitening in rabbits.Frontiers in cell and developmental biology · 2022Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adipogenesis is a multi-step process orchestrated by activation of numerous TFs, whose cooperation and regulatory network remain elusive. Activating transcription factor 4 (ATF4) is critical for adipogenesis, yet its regulatory network is unclarified. Here, we mapped genome-wide ATF4 binding landscape and its regulatory network by Chip-seq and RNA-seq and found ATF4 directly modulated transcription of genes enriching in fat cell differentiation. Motifs of TFs especially CTCF were found from ATF4 binding sites, suggesting a direct role of ATF4 in regulating adipogenesis associated with CTCF and other TFs. Deletion of CTCF attenuated adipogenesis while overexpression enhanced adipocyte differentiation, indicating CTCF is indispensable for adipogenesis. Intriguingly, combined analysis of Chip-seq data of these two TFs showed that ATF4 co-localized with CTCF in the promoters of key adipogenic genes including Cebpd and PPARg and co-regulated their transactivation. Moreover, ATF4 directly regulated CTCF expression and interacted with CTCF in differentiated 3T3-L1 cells. In vivo, downregulation of ATF4 suppressed the expression of CTCF, Cebpd, and PPARg, leading to reduced adipose tissue expansion in refeeding mice. Consistently, mRNA expression of ATF4 and CTCF was positively correlated with each other in human subcutaneous adipose tissue and inversely associated with BMI, indicating a possible involvement of these two TFs in adipose development. Taken together, our data propose for the first time that ATF4 and CTCF work cooperatively to control adipogenesis and adipose development via orchestrating transcription of adipogenic genes. Our findings reveal novel therapeutic targets in obesity treatment.
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