Role of the Isoforms of CCAAT/Enhancer-binding Protein in the Initiation of Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription at Birth

Croniger, Colleen M.; Trus, Michael; Lysek-Stupp, Keren; Cohen, Hannah; Liu, Yan; Darlington, Gretchen J.; Poli, Valeria; Hanson, Richard W.; Reshef, Lea

doi:10.1074/jbc.272.42.26306

Cited by 99 publications

(85 citation statements)

References 58 publications

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“…Direct C͞EBP␤ target genes in quiescent and regenerating liver identified by this combined screening method are listed in Table 1. Three of these [Aldh1a1 (24), Pepck (25,26), and Saa1 (27-29)] have been reported to be targets of C͞EBP␤, providing support for the utility of our orthogonal analysis.…”

Section: Resultsmentioning

confidence: 81%

Orthogonal analysis of C/EBPβ targets in vivo during liver proliferation

Friedman

Larris

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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CCAAT enhancer-binding protein ␤ (C͞EBP␤), a basic-leucine zipper transcription factor, is an important effector of signals in physiologic growth and cancer. The identification of direct C͞EBP␤ targets in vivo has been limited by functional compensation by other C͞EBP family proteins and the low stringency of the consensus sequence. Here we use the combined power of expression profiling and high-throughput chromatin immunoprecipitation to identify direct and biologically relevant targets of C͞EBP␤. We identified 25 potential C͞EBP␤ targets, of which 88% of those tested were confirmed as in vivo C͞EBP␤-binding sites. Six of these genes also displayed differential expression in C͞EBP␤ ؊/؊ livers. Computational analysis revealed that bona fide C͞EBP␤ target genes can be distinguished by the presence of binding motifs for specific additional transcription factors in the vicinity of the C͞EBP␤ site. This approach is generally applicable to the discovery of direct, biologically relevant targets of mammalian transcription factors.C CAAT enhancer-binding proteins (C͞EBPs) constitute a family of basic-leucine zipper (bZIP) transcription factors that are critical for the regulation of numerous biological processes, including differentiation, metabolic homeostasis, proliferation, tumorigenesis, inflammation, and apoptosis (1-9). C͞EBP proteins are regulated at multiple levels, including gene transcription, translation, and phosphorylation, in response to a variety of stimuli including hormonal, cytokine and growth factor-signaling pathways (1). C͞EBP proteins are able to form hetero-and homodimeric complexes with other C͞EBP family members, thereby creating additional diversity in target sequence recognition.C͞EBP␤ is an important effector of growth signals in experimental models of physiologic and neoplastic growth, the acutephase response, and metabolic homeostasis (1-11). Livers from C͞EBP␤ Ϫ/Ϫ mice exhibit a blunted regenerative response associated with prolonged hypoglycemia and altered expression of several cell-cycle-associated genes (10). In addition, a recent microarray analysis of human tumors has implicated C͞EBP␤ as a downstream mediator of cyclin D (12). Although these studies provide strong support for the role of C͞EBP␤ as a regulator of cell growth, at present, neither the mechanism by which C͞EBP␤ modulates the growth effects of cyclin D1 nor the targets of C͞EBP␤ in this pathway have been elucidated.A variety of approaches has been used to identify C͞EBP␤-binding sites, including cell culture systems, C͞EBP␤ Ϫ/Ϫ mice, and analyses of promoter sequences. However, several obstacles have limited the identification of direct C͞EBP␤-dependent transcriptional targets in vivo. All C͞EBP family members with the exception of C͞EBP possess identical in vitro DNA-binding affinity for C͞EBP consensus sequences, suggesting that other C͞EBP family members may be able to compensate for the loss of C͞EBP␤ (13). Second, the application of computational sequence analysis to identify C͞EBP promoter sequences has been impede...

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Section: Resultsmentioning

confidence: 81%

Orthogonal analysis of C/EBPβ targets in vivo during liver proliferation

Friedman

Larris

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…While both the ␣ and ␤ isoforms of C/EBP can have a role in the regulation of PEPCK expression, in vivo they are not functionally redundant. In C/EBP␣ knock-out mice, the PEPCK gene was not induced at birth although PEPCK expression did rise after several hours (17,18). In addition, the PEPCK gene was poorly responsive to cAMP (18).…”

Section: Reporter Vectormentioning

confidence: 94%

“…Our studies have defined various transcription factors involved in regulation by T 3 and cAMP. Previous work has focused on the role of C/EBP␣ in the T 3 and cAMP effects because C/EBP␣ is highly expressed in the liver and clearly contributes to the induction of PEPCK expression at birth (8,18,20). In this study, we have examined the contributions of C/EBP␤ to the basal expression and hormonal responsiveness of the PEPCK gene.…”

Section: Reporter Vectormentioning

confidence: 99%

“…C/EBP␣ is expressed primarily in liver and adipose tissue and regulates the expression of hepatic genes involved in energy metabolism (16,17). In addition to participating in hormonal responsiveness, C/EBP proteins play an important role in PEPCK gene transcription by contributing to the induction of the PEPCK gene at birth and directing liver-specific expression (11,17,18). Our early studies showed that C/EBP␣ and ␤ could bind to the CRE, P3(I), and P4(I) elements in the PEPCK promoter (15,19).…”

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confidence: 99%

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Role of CCAAT Enhancer-binding Protein β in the Thyroid Hormone and cAMP Induction of Phosphoenolpyruvate Carboxykinase Gene Transcription

Park

Song

Vinson

et al. 1999

Journal of Biological Chemistry

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“…C/EBP␤ is found to be constitutively expressed in the liver, intestine, lung, adipose tissue, spleen, and kidney (39 -43) and plays an important role in adipocyte (40,44), hepatocyte (45), and mammary gland differentiation (29), as well as in ovulation (32,46). C/EBP␤ knock-out mice (43) have alteration in glucose homeostasis (47), immunological defects (48), develop lymphoproliferative disorders (49,50) and defects in female reproduction and infertility (32). The participation of C/EBP␤ in so many diverse pathways suggests that multiple levels of regulation contribute to its various biological functions.…”

Section: Discussionmentioning

confidence: 99%

C/EBPβ Participates in Regulating Transcription of the p53 Gene in Response to Mitogen Stimulation

Boggs

Reisman

2007

Journal of Biological Chemistry

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The tightly regulated expression of p53 contributes to genomic stability, and transcription of the p53 gene is induced prior to cells entering S phase, possibly as a mechanism to ensure a rapid p53 response in the event of DNA damage. We have previously described the cloning of an additional 1000 bp of upstream p53 sequences that we have demonstrated play a role in the regulated expression of p53. As described in an earlier report, we preliminarily identified that a member of the CAAT/ enhancer-binding protein (C/EPB) family of transcription factors may play a role in regulating p53. Here we have demonstrated that a particular C/EBP␤ isoform, C/EBP␤-2, efficiently binds to the p53 promoter and induces its expression in a fashion that reflects the pattern of p53 expression seen as cells are induced to enter S phase and is absent from cells that are defective in proper p53 regulation. We conclude from these findings that C/EBP␤-2 plays a central role in the regulating of p53 transcription during the transition into S phase.

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Role of the Isoforms of CCAAT/Enhancer-binding Protein in the Initiation of Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription at Birth

Cited by 99 publications

References 58 publications

Orthogonal analysis of C/EBPβ targets in vivo during liver proliferation

Orthogonal analysis of C/EBPβ targets in vivo during liver proliferation

Role of CCAAT Enhancer-binding Protein β in the Thyroid Hormone and cAMP Induction of Phosphoenolpyruvate Carboxykinase Gene Transcription

C/EBPβ Participates in Regulating Transcription of the p53 Gene in Response to Mitogen Stimulation

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