ArticleThe Journal of biological chemistry2011
Additional sex comb-like (ASXL) proteins 1 and 2 play opposite roles in adipogenesis via reciprocal regulation of peroxisome proliferator-activated receptor {gamma}.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- BAP1 Loss Affords Lipotoxicity Resistance in Uveal Melanoma.Pigment cell & melanoma research · 2025Article
- Asxl1 loss in mice leads to microcephaly by regulating neural stem cell survival.Animal cells and systems · 2025Article
- Integrative analysis of ASXL family genes reveals ASXL2 as an immunoregulatory molecule in head and neck squamous cell carcinoma.Scientific reports · 2024Article
- ASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers.Nature communications · 2024Article
- Additional Sex Combs-like Family Associated with Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Epigenetic regulation by ASXL1 in myeloid malignancies.International journal of hematology · 2023Review
- RINGs, DUBs and Abnormal Brain Growth-Histone H2A Ubiquitination in Brain Development and Disease.Epigenomes · 2022Review
- ASXL1/2 mutations and myeloid malignancies.Journal of hematology & oncology · 2022Review
- High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism.Nutrients · 2022Article
- PGC-1: a key regulator in bone homeostasis.Journal of bone and mineral metabolism · 2022Review
- The genetics of myelodysplastic syndromes and the opportunities for tailored treatments.Frontiers in oncology · 2022Review
- Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.Journal of biomedical science · 2021Article
- Review
- A Broad Overview of Signaling inCancers · 2021Review
- Clinical implication and prognostic significance of FLT3-ITD and ASXL1 mutations in Egyptian AML patients: A single-center study.Cancer biomarkers : section A of Disease markers · 2021Article
- Association between serum anti‑ASXL2 antibody levels and acute ischemic stroke, acute myocardial infarction, diabetes mellitus, chronic kidney disease and digestive organ cancer, and their possible association with atherosclerosis and hypertension.International journal of molecular medicine · 2020Article
- The tale of two genes: from next-generation sequencing to phenotype.Cold Spring Harbor molecular case studies · 2020Article
- Elevated Expression of ASXL2 is Associated with Poor Prognosis in Colorectal Cancer by Enhancing Tumorigenesis and Inducing Cell Proliferation.Cancer management and research · 2020Article
- Comparative Study of PPARPPAR research · 2020Article
- Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous studies have suggested that the mammalian additional sex comb-like 1 protein functions as a coactivator or repressor of retinoic acid receptors in a cell-specific manner. Here, we investigated the roles of additional sex comb-like 1 proteins in regulating peroxisome proliferator-activated receptors (PPARs). In pulldown assays in vitro and in immunoprecipitation assays in vivo, ASXL1 and its paralog, ASXL2, interacted with PPARα and PPARγ. In 3T3-L1 preadipocyte cells, overexpression of ASXL1 inhibited the induction of PPARγ activity by rosiglitazone, as shown by transcription assays, and completely suppressed adipogenesis, as shown by Oil Red O staining. In contrast, overexpression of ASXL2 greatly enhanced rosiglitazone-induced PPARγ activity and enhanced adipogenesis. Deletion of the heterochromatin protein 1 (HP1)-binding domain from ASXL1 caused the mutant protein to enhance adipogenesis similarly to ASXL2, indicating that HP1 binding is required for the adipogenesis-suppressing activity of ASXL1. Adipocyte differentiation was associated with a gradual decrease in ASXL1 expression but did not affect ASXL2 expression. Knockdown of ASXL1 and ASXL2 had reciprocal effects on adipogenesis. In chromatin immunoprecipitation assays in 3T3-L1 cells, ASXL1 occupied the promoter of the PPARγ target gene aP2 together with HP1α and Lys-9-methylated histone H3, whereas ASXL2 occupied the aP2 promoter together with histone-lysine N-methyltransferase MLL1 and Lys-9-acetylated and Lys-4-methylated H3 histones. Finally, microarray analysis demonstrated that ASXL1 represses, whereas ASXL2 increases, the expression of adipogenic genes, most of which are PPARγ targets. These results suggest that members of the additional sex comb-like family provide complex regulation of adipogenesis via differential modulation of PPARγ activity.
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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.