Propagation of Adipogenic Signals Through an Epigenomic Transition State

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2010 May 19

PMID 20478996

Citations 154

Authors

David J Steger

Gregory R Grant

Michael Schupp

Takuya Tomaru

Martina I Lefterova

Jonathan Schug

Elisabetta Manduchi

Christian J Stoeckert Jr

Mitchell A Lazar

Affiliations

Soon will be listed here.

Abstract

The transcriptional mechanisms by which temporary exposure to developmental signals instigates adipocyte differentiation are unknown. During early adipogenesis, we find transient enrichment of the glucocorticoid receptor (GR), CCAAT/enhancer-binding protein beta (CEBPbeta), p300, mediator subunit 1, and histone H3 acetylation near genes involved in cell proliferation, development, and differentiation, including the gene encoding the master regulator of adipocyte differentiation, peroxisome proliferator-activated receptor gamma2 (PPARgamma2). Occupancy and enhancer function are triggered by adipogenic signals, and diminish upon their removal. GR, which is important for adipogenesis but need not be active in the mature adipocyte, functions transiently with other enhancer proteins to propagate a new program of gene expression that includes induction of PPARgamma2, thereby providing a memory of the earlier adipogenic signal. Thus, the conversion of preadipocyte to adipocyte involves the formation of an epigenomic transition state that is not observed in cells at the beginning or end of the differentiation process.

Citing Articles

Preliminary study of the role of histone deacetylase (HDAC) in steroid-induced avascular necrosis of the femoral head induced by BMSC adipogenic differentiation.

Yu Y, Duan P, Zheng L, Xu J, Pan Z J Orthop Surg Res. 2024; 19(1):645.

PMID: 39396027 PMC: 11481159. DOI: 10.1186/s13018-024-05121-z.

Assessing Receptor Activation in 2D and 3D Cultured Hepatocytes: Responses to a Single Compound and a Complex Mixture.

Jamshed L, Jamshed S, Frank R, Hewitt L, Thomas P, Holloway A Toxics. 2024; 12(9).

PMID: 39330559 PMC: 11436198. DOI: 10.3390/toxics12090631.

IL-1β promotes adipogenesis by directly targeting adipocyte precursors.

Hofwimmer K, de Paula Souza J, Subramanian N, Vujicic M, Rachid L, Mereau H Nat Commun. 2024; 15(1):7957.

PMID: 39261467 PMC: 11390900. DOI: 10.1038/s41467-024-51938-x.

Role of Na/K-ATPase α1 caveolin-binding motif in adipogenesis.

Huang M, Wang X, Chen Y, Pessoa M, Terrell K, Zhang J Am J Physiol Cell Physiol. 2024; 327(1):C48-C64.

PMID: 38708522 PMC: 11371328. DOI: 10.1152/ajpcell.00168.2024.

14-3-3ζ regulates adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation.

Rial S, You Z, Vivoli A, Sean D, Al-Khoury A, Lavoie G bioRxiv. 2024; .

PMID: 38562727 PMC: 10983991. DOI: 10.1101/2024.03.18.585495.

References

Wang Z, Zang C, Rosenfeld J, Schones D, Barski A, Cuddapah S . Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008; 40(7):897-903. PMC: 2769248. DOI: 10.1038/ng.154. View

Lupien M, Eeckhoute J, Meyer C, Wang Q, Zhang Y, Li W . FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell. 2008; 132(6):958-70. PMC: 2323438. DOI: 10.1016/j.cell.2008.01.018. View

Lefterova M, Zhang Y, Steger D, Schupp M, Schug J, Cristancho A . PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev. 2008; 22(21):2941-52. PMC: 2577797. DOI: 10.1101/gad.1709008. View

Hassan A, Neely K, Vignali M, Reese J, Workman J . Promoter targeting of chromatin-modifying complexes. Front Biosci. 2001; 6:D1054-64. DOI: 10.2741/hassan. View

Thomas P, Kejariwal A, Guo N, Mi H, Campbell M, Muruganujan A . Applications for protein sequence-function evolution data: mRNA/protein expression analysis and coding SNP scoring tools. Nucleic Acids Res. 2006; 34(Web Server issue):W645-50. PMC: 1538848. DOI: 10.1093/nar/gkl229. View

Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni J, Gygi S . Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature. 2009; 460(7259):1154-8. PMC: 2754867. DOI: 10.1038/nature08262. View

Wiper-Bergeron N, Abdou Salem H, Tomlinson J, Wu D, Hache R . Glucocorticoid-stimulated preadipocyte differentiation is mediated through acetylation of C/EBPbeta by GCN5. Proc Natl Acad Sci U S A. 2007; 104(8):2703-8. PMC: 1815245. DOI: 10.1073/pnas.0607378104. View

Wu Z, Rosen E, Brun R, Hauser S, Adelmant G, Troy A . Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell. 1999; 3(2):151-8. DOI: 10.1016/s1097-2765(00)80306-8. View

Pantoja C, Huff J, Yamamoto K . Glucocorticoid signaling defines a novel commitment state during adipogenesis in vitro. Mol Biol Cell. 2008; 19(10):4032-41. PMC: 2555927. DOI: 10.1091/mbc.e08-04-0420. View

10.

Visel A, Blow M, Li Z, Zhang T, Akiyama J, Holt A . ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature. 2009; 457(7231):854-8. PMC: 2745234. DOI: 10.1038/nature07730. View

11.

Peeke P, Chrousos G . Hypercortisolism and obesity. Ann N Y Acad Sci. 1995; 771:665-76. DOI: 10.1111/j.1749-6632.1995.tb44719.x. View

12.

Bernstein B, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey D, Huebert D . Genomic maps and comparative analysis of histone modifications in human and mouse. Cell. 2005; 120(2):169-81. DOI: 10.1016/j.cell.2005.01.001. View

13.

Thomas P, Campbell M, Kejariwal A, Mi H, Karlak B, Daverman R . PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 2003; 13(9):2129-41. PMC: 403709. DOI: 10.1101/gr.772403. View

14.

Farmer S . Transcriptional control of adipocyte formation. Cell Metab. 2006; 4(4):263-73. PMC: 1958996. DOI: 10.1016/j.cmet.2006.07.001. View

15.

Ji H, Jiang H, Ma W, Johnson D, Myers R, Wong W . An integrated software system for analyzing ChIP-chip and ChIP-seq data. Nat Biotechnol. 2008; 26(11):1293-300. PMC: 2596672. DOI: 10.1038/nbt.1505. View

16.

Boyer L, Lee T, Cole M, Johnstone S, Levine S, Zucker J . Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005; 122(6):947-56. PMC: 3006442. DOI: 10.1016/j.cell.2005.08.020. View

17.

Alon U . Network motifs: theory and experimental approaches. Nat Rev Genet. 2007; 8(6):450-61. DOI: 10.1038/nrg2102. View

18.

Pijl H, Meinders A . Bodyweight change as an adverse effect of drug treatment. Mechanisms and management. Drug Saf. 1996; 14(5):329-42. DOI: 10.2165/00002018-199614050-00005. View

19.

Mangan S, Alon U . Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci U S A. 2003; 100(21):11980-5. PMC: 218699. DOI: 10.1073/pnas.2133841100. View

20.

Tanaka T, Yoshida N, Kishimoto T, Akira S . Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO J. 1998; 16(24):7432-43. PMC: 1170343. DOI: 10.1093/emboj/16.24.7432. View