ArticleThe Journal of biological chemistry2022
Transcription factors KLF15 and PPARδ cooperatively orchestrate genome-wide regulation of lipid metabolism in skeletal muscle.
Article in The Journal of biological chemistry, 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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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Circulating factors induced by time-restricted eating drive metabolic reprogramming in endothelial cells.GeroScience · 2026Article
- KLF transcription factors in metabolic kidney disease: from podocyte protection to tubulointerstitial fibrosis.International urology and nephrology · 2026Review
- Comprehensive Identification of the Bovine KLF Gene Family and Its Functional Regulation in Muscle Development: Insights from Single-Nuclei Transcriptomics.Animals : an open access journal from MDPI · 2025Article
- Effect ofInternational journal of molecular sciences · 2025Review
- Integration of whole genome resequencing and transcriptome sequencing to identify candidate genes for tall and short traits in Baicheng Fatty chickens.Frontiers in veterinary science · 2025Article
- Krüppel-like factors family in health and disease.MedComm · 2024Review
- Article
- The genetic regulatory architecture and epigenomic basis for age-related changes in rattlesnake venom.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis.Open life sciences · 2024Article
- An Overview of the Role of Peroxisome Proliferator-activated Receptors in Liver Diseases.Journal of clinical and translational hepatology · 2023Review
- Empagliflozin induces the transcriptional program for nutrient homeostasis in skeletal muscle in normal mice.Scientific reports · 2023Article
- Efficacy/Safety of the Use of Glucocorticoids in Oral and Maxillofacial Surgery.Dentistry journal · 2023Review
- Krüppel-like Factor 15 Suppresses Ferroptosis by Activating an NRF2/GPX4 Signal to Protect against Folic Acid-Induced Acute Kidney Injury.International journal of molecular sciences · 2023Article
- Exercise metabolism and adaptation in skeletal muscle.Nature reviews. Molecular cell biology · 2023Review
- Epigenomics Analysis of the Suppression Role ofInternational journal of molecular sciences · 2023Article
- Genome-Wide Analysis of theAnimals : an open access journal from MDPI · 2023Article
- Specificity Proteins (SP) and Krüppel-like Factors (KLF) in Liver Physiology and Pathology.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Skeletal muscle dynamically regulates systemic nutrient homeostasis through transcriptional adaptations to physiological cues. In response to changes in the metabolic environment (e.g., alterations in circulating glucose or lipid levels), networks of transcription factors and coregulators are recruited to specific genomic loci to fine-tune homeostatic gene regulation. Elucidating these mechanisms is of particular interest as these gene regulatory pathways can serve as potential targets to treat metabolic disease. The zinc-finger transcription factor Krüppel-like factor 15 (KLF15) is a critical regulator of metabolic homeostasis; however, its genome-wide distribution in skeletal muscle has not been previously identified. Here, we characterize the KLF15 cistrome in vivo in skeletal muscle and find that the majority of KLF15 binding is localized to distal intergenic regions and associated with genes related to circadian rhythmicity and lipid metabolism. We also identify critical interdependence between KLF15 and the nuclear receptor PPARδ in the regulation of lipid metabolic gene programs. We further demonstrate that KLF15 and PPARδ colocalize genome-wide, physically interact, and are dependent on one another to exert their transcriptional effects on target genes. These findings reveal that skeletal muscle KLF15 plays a critical role in metabolic adaptation through its direct actions on target genes and interactions with other nodal transcription factors such as PPARδ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.