Function of GATA Transcription Factors in Preadipocyte-Adipocyte Transition

Tong, Qiang; Dalgin, Gökhan; Xu, Haiyan; Ting, Chao-Nan; Leiden, Jeffrey M.; Hotamışlıgil, Gökhan S.

doi:10.1126/science.290.5489.134

Cited by 462 publications

(374 citation statements)

References 20 publications

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“…HDACs are enzymes that play an important role in the regulation of gene expression and are best known for their role in repressing gene transcription via interaction with transcriptional repressors [Ng and Bird, 2000]. Interestingly, both HDACs and transcriptional repressors have previously been implicated in the regulation of adipocyte differentiation: HDAC-1 has been shown to associate with the C/EBPa promoter and play an important role in preventing C/EBPa expression in unstimulated preadipocytes [Wiper-Bergeron et al, 2003], while a number of transcriptional repressors have been implicated in the regulation of adipogenesis via the direct inhibition of both C/EBPa and PPARg gene expression [Tong et al, 2000;Yun et al, 2002;Banerjee et al, 2003;Shi et al, 2003]. Hence, it is tempting to speculate that one potential mechanism by which the PGF2a-calcineurin signaling pathway may inhibit adipocyte differentiation is by inducing the expression and/or activity of an HDAC-associated transcriptional repressor that is either able to directly inhibit the expression of the PPARg and C/EBPa genes, or alternatively, acts indirectly, by inhibiting the expression of a gene(s) that is normally required to promote the expression of PPARg and C/ EBPa.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Liu

Clipstone

2006

J of Cellular Biochemistry

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Prostaglandin F2a (PGF2a) is a potent physiological inhibitor of adipocyte differentiation, however the specific signaling pathways and molecular mechanisms involved in mediating its anti-adipogenic effects are not well understood. In the current study, we now provide evidence that PGF2a inhibits adipocyte differentiation via a signaling pathway that requires heterotrimeric G-protein Gaq subunits, the elevation of the intracellular calcium concentration ([Ca 2þ ] i ), and the activation of the Ca 2þ /calmodulin-regulated serine/threonine phosphatase calcineurin. We show that while this pathway acts to inhibit an early step in the adipogenic cascade, it does not interfere with the initial mitotic clonal expansion phase of adipogenesis, nor does it affect either the expression, DNA binding activity or differentiation-induced phosphorylation of the early transcription factor C/EBPb. Instead, we find that PGF2a inhibits adipocyte differentiation via a calcineurin-dependent mechanism that acts to prevent the expression of the critical pro-adipogenic transcription factors PPARg and C/EBPa. Furthermore, we demonstrate that the inhibitory effects of PGF2a on both the expression of PPARg and C/EBPa and subsequent adipogenesis can be attenuated by treatment of preadipocytes with the histone deacetylase (HDAC) inhibitor trichostatin A. Taken together, these results indicate that PGF2a inhibits adipocyte differentiation via a Gaq-Ca 2þ -calcineurin-dependent signaling pathway that acts to block expression of PPARg and C/EBPa by a mechanism that appears to involves an HDAC-sensitive step.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Liu

Clipstone

2006

J of Cellular Biochemistry

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“…In particular, constitutive expression of GATA-2 and GATA-3 was shown to decrease PPARg expression and, as a consequence, inhibition of adipocyte differentiation. 7 Other transcription factors, such as TCF4, a transcriptional mediator of the Wnt pathway, were suggested to repress PPARg and C/EBPa expression in preadipocytes. 8 Among the activators of PPARg expression, the CCAAT enhancer-binding proteins (C/EBP) are possibly the most studied.…”

Section: Regulation Of Pparc Expressionmentioning

confidence: 99%

Atypical transcriptional regulators and cofactors of PPARγ

Miard

Fajas

2005

Int J Obes

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Regulation of peroxisome proliferator-activated receptor gamma (PPARg) activity is the result of several events. The first control level is the regulation of the expression of PPARg. Examples of this regulation, during adipogenesis, is the transactivation of the PPARg promoter by transcription factors of the classical pathway, such as C/EBPs or ADD1/SREBP1, but also newly identified factors, such as E2Fs. When preadipocytes re-enter the cell cycle, PPARg expression is induced coincident with an increase in DNA synthesis, suggesting the involvement of the E2F family of cell cycle regulators. E2F1 induces PPARg transcription during clonal expansion, whereas E2F4 represses PPARg expression during terminal adipocyte differentiation. Hence, E2Fs represent the link between proliferative signaling pathways, triggering clonal expansion, and terminal adipocyte differentiation through regulation of PPARg expression. A second regulatory level of PPARg action is interaction with cofactors. We will focus our attention on the atypical PPARg modulators. We have described an interaction between PPARg and the retinoblastoma protein, RB, which is both dependent upon ligand binding by PPARg and upon the phosphorylation status of RB. The interaction between PPARg and RB decreases the transcriptional activity of PPARg through recruitment of the histone deacetylase HDAC3. Inhibition of HDAC activity consequently results in a strong activation of PPARg.

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“…In addition, heterozygous Pparg-deficient mice were less susceptible to insulin resistance due to adipocyte hypertrophy suggesting reduced Pparg expression was protective [Kubota et al, 1999]. Multiple reports have documented that activated PPARG induces the expression of genes involved in lipid metabolism in both skeletal muscle and adipose tissue [Lowell, 1999;Tong et al, 2000;Rosen et al, 2002]. Furthermore, an inverse relationship between the PPARG1 isoform expression in adipose tissue and body mass index (BMI) has been shown but not for the PPARG2 isoform [Sewter et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

A 9‐year‐old male with a duplication of chromosome 3p25.3p26.2: Clinical report and gene expression analysis

Bittel

Kibiryeva

Dasouki

et al. 2006

American J of Med Genetics Pt A

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We describe a 9-year-old male referred for genetic evaluation for Prader-Willi syndrome (PWS). PWS is the most common genetically-defined cause of life-threatening obesity and results from a functional loss of paternally-expressed genes from the chromosome 15q11-q13 region. The patient presented with pervasive developmental disorder, delayed speech and rapid onset of obesity at age 4 years, all features similar to PWS. However, chromosome 15q11-q13 methylation testing and fragile X studies were normal. GTG-banding and fluorescence in situ hybridization with whole chromosome 3 paint probe and a chromosome 3p subtelomeric probe suggested a duplication of 3p25.3p26.2, a finding supported by comparative genomic hybridization. This region of chromosome 3p contains genes which contribute to obesity and behavioral problems, most notably, ghrelin (GHRL), an oxytocin receptor (OXTR), solute carrier family 6 members (GABA neurotransmitter transporters, SLC6A1 and SLC6A11) and peroxisome proliferator-activated receptor, gamma (PPARG). To characterize these obesity and behavior related genes in our subject, we performed quantitative RT-PCR and compared expression levels with similarly aged male subjects (four nonobese males, four obese males and four PWS males -two with 15q11-q13 deletions and two with maternal disomy 15). Our studies suggest increased expression of several genes in the 3p duplication region, including GHRL and PPARG, which may contribute to the phenotypic features in our 3p duplication subject.

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Function of GATA Transcription Factors in Preadipocyte-Adipocyte Transition

Cited by 462 publications

References 20 publications

Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Prostaglandin F2α inhibits adipocyte differentiation via a Gαq‐Calcium‐Calcineurin‐Dependent signaling pathway

Atypical transcriptional regulators and cofactors of PPARγ

A 9‐year‐old male with a duplication of chromosome 3p25.3p26.2: Clinical report and gene expression analysis

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