Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins.

Yeh, Wen-Chen; Cao, Zhaodan; Classon, Marie; McKnight, Steven L.

doi:10.1101/gad.9.2.168

Cited by 845 publications

(766 citation statements)

References 57 publications

(59 reference statements)

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“…Therefore, the entire Mad gene family is not expressed in every di erentiating tissue and may require cell-type speci®c cues. These results also strongly suggest that the transcription of individual Mad genes does not depend on prior expression of other Mad family members, and that their sequential expression is not a true cascade as such has been demonstrated for myogenic transcription activators and the C/EBPs (Weintraub, 1993;Yeh et al, 1995). As the MAD proteins function as transcriptional repressors, the opposite situation, in which cross downregulation occurs might be expected.…”

Section: Sequential Expression Of Mad Family Genessupporting

confidence: 54%

Sequential expression of the MAD family of transcriptional repressors during differentiation and development

et al. 1998

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Members of the Myc proto-oncogene family encode transcription factors that function in multiple aspects of cell behavior, including proliferation, di erentiation, transformation and apoptosis. Recent studies have shown that MYC activities are modulated by a network of nuclear bHLH-Zip proteins. The MAX protein is at the center of this network in that it associates with MYC as well as with the family of MAD proteins: MAD1, MXI1, MAD3 and MAD4. Whereas MYC ± MAX complexes activate transcription, MAD ± MAX complexes repress transcription through identical E-box binding sites. MAD proteins therefore act as antagonists of MYC. Here we report the expression patterns of the Mad gene family in the adult and developing mouse. High level of Mad gene expression in the adult is limited to tissues that display constant renewal of di erentiated cell populations. In embryos, Mad transcripts are widely distributed with expression peaking during organogenesis at the onset of di erentiation. A detailed analysis of their pattern of expression during chrondrocyte and neuronal di erentiation in vivo, and during neuronal di erentiation of P19 cells in vitro, shows that Mad family genes are sequentially induced. Mad3 transcripts and proteins are detected in proliferating cells prior to di erentiation. Mxi1 and Mad4 transcripts are most abundant in cells that have further advanced along the di erentiation pathway, whereas Mad1 is primarily expressed late in di erentiation. Taken together, our data suggest that the di erent members of the MAD protein family exert their functions at distinct steps during the transition between proliferation and di erentiation.

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Section: Sequential Expression Of Mad Family Genessupporting

confidence: 54%

Sequential expression of the MAD family of transcriptional repressors during differentiation and development

et al. 1998

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“…Studies in adipogenic cell lines have shown that hormonal induction of differentiation is rapidly followed by expression of C/EBPb, C/EBPd, PPARg and C/EBPa. 5,6 PPARg and C/EBPa induce each other's expression through a positive feedback loop. 7 The latter factors drive the expression of genes that are necessary for lipid synthesis.…”

Section: Introductionmentioning

confidence: 99%

Hypertrophy and hyperplasia of abdominal adipose tissues in women

et al. 2007

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Objective: To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue. Research design and methods: We obtained subcutaneous and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 4775 years; BMI 27.975.3 kg/m 2 ). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation and body fat distribution were obtained (dual-energy X-ray absorptiometry and computed tomography, respectively). Results: Adipocyte size of both subcutaneous and omental fat were increased with higher body fat mass values, with similar regression slopes in each compartment. In contrast, with higher body fat mass values, fat accumulation was progressively higher in the subcutaneous than in the visceral fat compartment, suggesting hyperplasia in the subcutaneous fat compartment. Messenger RNA levels of CEBPa, PPARg2, SREBP1c and genes related to lipid metabolism (LPL, FABP4, DGAT1, DGAT2, PLIN and HSL) were significantly higher in subcutaneous than in omental fat tissue (Pp0.001 for all). Only subcutaneous expression of these genes tracked with obesity levels as reflected by significant positive associations between subcutaneous fat CEBPa, SREBP1c and DGAT2 expression and total body fat mass (r ¼ 0.37, r ¼ 0.41, r ¼ 0.57, respectively, Pp0,05), fat percentage (r ¼ 0.40, r ¼ 0.39, r ¼ 058, respectively, Pp0,05) and subcutaneous adipose tissue area (r ¼ 0.36, r ¼ 0.38, r ¼ 0.58, respectively, Pp0,05). Omental adipose tissue expression levels of these genes were not significantly related to adiposity measures. Conclusions: These results show that in obese women, hyperplasia is predominant in the subcutaneous fat depot, whereas fat cell hypertrophy is observed both in the omental and subcutaneous compartments.

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“…Members of the C/EBP family are known to have an essential role in adipose tissue development (Cao et al, 1991;Samuelsson et al, 1991;Umek et al, 1991;Freytag and Geddes, 1992;Wang et al, 1995;Yeh et al, 1995) and FUS-CHOP blocks di erentiation of adipogenic precursors in tissue culture (Kuroda et al, 1997;Adelmant et al, 1998). Whereas interference with the normal process of di erentiation may contribute to the oncogenic potential of FUS-CHOP fusion protein, it is a property that they share with the nontransforming germline CHOP gene product (Zinszner et al, 1994;Batchvarova et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice

et al. 2000

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The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that encodes the FUS-CHOP chimeric protein, is associated with human liposarcomas. The altered expression of FUS-CHOP has been implicated in a characteristic subgroup of human liposarcomas. We have introduced the FUS-CHOP transgene into the mouse genome in which the expression of the transgene is successfully driven by the elongation factor 1a (EF1a) promoter to all tissues. The consequent overexpression of FUS-CHOP results in most of the symptoms of human liposarcomas, including the presence of lipoblasts with round nuclei, accumulation of intracellular lipid, induction of adipocyte-speci®c genes and a concordant block in the di erentiation program. We have demonstrated that liposarcomas in the FUS-CHOP transgenic mice express high levels of the adipocyte regulatory protein PPARg, whereas it is not expressed in embryonic ®broblasts from these animals following induction to di erentiation toward the adipocyte lineage, indicating that the in vitro system does not really re¯ect the in vivo situation and the developmental defect is downstream of PPARg expression. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1a promoter. This establishes FUS-CHOP overexpression as a key determinant of human liposarcomas and provide the ®rst in vivo evidence for a link between a fusion gene created by a chromosomal translocation and a solid tumor.

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Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins.

Cited by 845 publications

References 57 publications

Sequential expression of the MAD family of transcriptional repressors during differentiation and development

Sequential expression of the MAD family of transcriptional repressors during differentiation and development

Hypertrophy and hyperplasia of abdominal adipose tissues in women

The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice

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