Hepatocyte Nuclear Factor-1α Recruits the Transcriptional Co-Activator p300 on the GLUT2 Gene Promoter

Ban, Nobuhiro; Yamada, Yoshio; Someya, Yoshimichi; Miyawaki, Kazumasa; Ihara, Yu; Hosokawa, Munetaka; Toyokuni, Shinya; Tsuda, Kinsuke; Seino, Yutaka

doi:10.2337/diabetes.51.5.1409

Cited by 82 publications

(68 citation statements)

References 30 publications

(21 reference statements)

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“…The results indicated that p300 did not enhance NF1-and HNF1␣-mediated activation of the L-PK promoter. 3 The reason for this is unclear, because p300 has been reported to interact with the activation domain of HNF1␣ (39). However, it is possible that other co-activators are involved in cooperative activation of the L-PK gene.…”

Section: Discussionmentioning

confidence: 84%

“…Thus, we consider the interesting possibility that NF1 family members function as coactivators of HNF1␣, although this issue must be further addressed in future studies. There are co-activators with histone acetyltransferase activity that can physically interact with HNF1␣ (38,39). They include p300/cAMP-response element-binding protein, p300/cAMP-response element-binding protein-associated factor, receptor-associated co-activator 3, and steroid receptor co-activator-1.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nuclear Factor 1 Family Members Interact with Hepatocyte Nuclear Factor 1α to Synergistically Activate L-type Pyruvate Kinase Gene Transcription

Satoh

Noaki

Ishigure

et al. 2005

Journal of Biological Chemistry

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Transcription of hepatic L-type pyruvate kinase (L-PK) gene is cell type-specific and is under the control of various nutritional conditions. The L-PK gene contains multiple cis-regulatory elements located within a 170-bp upstream region necessary for these regulations. These elements can synergistically stimulate L-PK gene transcription, although their mechanisms are largely unknown. Because nuclear factor (NF) 1 family members bind to specific cisregulatory elements known as L-IIA and L-IIB and hepatocyte nuclear factor (HNF) 1␣ binds to the adjacent element L-I, we examined the functional and physical interactions between these two transcription factors. Reporter gene assay showed that these two factors synergistically activated the L-PK promoter containing the 5-flanking region up to ؊189. Although two NF1-binding sites are required for the maximum synergistic effect of NF1 family members with HNF1␣, significant functional interaction between the two factors was observed in the L-PK promoter containing two mutated NF1-binding sites and also in the promoter containing only the HNF1␣-binding site, raising the possibility that NF1 proteins function as HNF1␣ co-activators. Chromatin immunoprecipitation assay revealed that both NF1 proteins and HNF1␣ bound to the promoter region of the L-PK gene in vivo. In vitro binding assay confirmed that NF1 proteins directly interacted mainly with the homeodomain of HNF1␣ via their DNA-binding domains. This interaction enhanced HNF1␣ binding to the L-I element and was also observed in rat liver by co-immunoprecipitation assay. Thus, we conclude that cooperative interaction between NF1 family members and HNF1␣ plays an important role in hepatic L-PK transcription.Pyruvate kinase (ATP, pyruvate 2-O-phosphotransferase; PK) 2 is an important regulatory enzyme in the glycolytic pathway. Four PK isozymes are known to exist in mammals and are designated as L, R, M 1 , and M 2 types (1). They are produced from two genes, PKL and PKM, by alternative use of two promoters and mutually exclusive alternative splicing, respectively (2-4). The L-type isozyme (L-PK) is expressed in a tissue-specific manner; this form is expressed primarily in hepatic parenchymal cells and is also present in pancreatic ␤ cells, kidney, and small intestine (1). Hepatic L-PK gene expression is also transcriptionally controlled positively by glucose in the presence of insulin and negatively by polyunsaturated fatty acids or glucagon via cyclic AMP (5-8). These regulations of the L-PK gene transcription are mediated via the multiple cis-regulatory elements located within a 170-bp upstream region from the transcription start site, as shown in Fig. 1 (8 -10). We have named these elements L-I (Ϫ94 to Ϫ76), L-II (Ϫ149 to Ϫ126), and L-III (Ϫ170 to Ϫ150) (9). In addition, another group has identified a weak negative element (Ϫ116 to Ϫ99) between L-I and L-II (10). Although this element has been named L2, we will refer to this as L-IIA and L-II as L-IIB hereafter. Although L-IIB is considered to be a regulatory element...

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Nuclear Factor 1 Family Members Interact with Hepatocyte Nuclear Factor 1α to Synergistically Activate L-type Pyruvate Kinase Gene Transcription

Satoh

Noaki

Ishigure

et al. 2005

Journal of Biological Chemistry

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“…As p300 has been reported to act as a transcription coactivator for HNF-1α [17], we next studied whether R263L and p300 could cooperatively enhance GLUT2 promoter activity in NIH3T3 cells that has a low p300 expression. Cotransfection of p300 increased GLUT2 promoter activity compared with WT HNF-1α transfection alone.…”

Section: Resultsmentioning

confidence: 99%

“…p300 or CBP also acts as a molecular bridge between transcriptional factors by binding to the activation domain of some transcriptional factors such as CREB as well as multiple components of the basal transcriptional machinery including RNA polymerase II complex [24]. As R263 is not in a region of HNF-1α interacting with p300 that binds to the transactivation domain of HNF-1α [17] and HNF-1α and -1β will interact with each other through their dimerization domains, the R263L mutation should not impair interactions between HNF-1α and p300 or HNF-1β, partly explaining why cotransfection of HNF-1β or p300 increases transcriptional activity of R263L mutant. However, the decreased activity of R263L mutant was not fully rescued by the coexpression with HNF-1β or p300 because R263 in HNF-1α contacts DNA directly regardless of its binding to HNF-1β or p300.…”

Section: Discussionmentioning

confidence: 99%

Identification and functional characterization of a novel mutation of hepatocyte nuclear factor-1α gene in a Korean family with MODY3

et al. 2003

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Aims/hypothesis. After screening 16 Korean families with early onset Type 2 diabetes in search for hepatocyte nuclear factor (HNF)-1α gene mutation, we identified a novel missense mutation (R263L) associated with MODY phenotype. We studied the biological characteristics of the mutation and the potential functional consequences based on the crystallographic structure of HNF-1α in complex with DNA. Methods. DNA from subjects with a familial form of early onset diabetes was isolated and HNF-1α was sequenced. The R263L substitution was generated by PCR-based sited-directed mutagenesis. Functional and biochemical studies were conducted by reporter assay using glucose-transporter type 2 (GLUT2) or insulin promoters and electrophoretic mobility shift assay, respectively. Results. Transfection of wild-type HNF-1α increased the reporter activities of GLUT2 and insulin promoters in NIH3T3 and SK-Hep1 cells, while R263L mutant was defective in transactivation of those promoters. Both wild-type HNF-1α and R263L mutant could not transactivate GLUT2 and insulin promoters in MIN6N8 insulinoma cells. R263L mutant had a defective cooperation with its heterodimeric partner HNF-1β or coactivator p300. R263L mutant protein displayed greatly reduced DNA binding ability, despite its comparable protein stability to the wild-type HNF-1α. Conclusion/interpretation. These results suggest that the mutation of HNF-1α at codon 263 from arginine to leucine leads to the development of MODY3 through decreased insulin production and defective glucose sensing. These findings are in good agreement with the crystal structure in which R263 makes hydrogen bonds with phosphorus atoms of DNA backbone to mediate the stable binding of HNF-1α homeodomain to the promoter. [Diabetologia (2003) 46:721-727]

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“…Moreover, curcumin decreases diabetes-induced oxidative stress in the kidney through reversion of p300 up-regulation in STZ-treated rats (Chiu et al 2009). Indeed, it has been suggested that abnormal interactions between mutant transcription factors and p300 contribute to the pathogenesis of diabetes (Eeckhoute et al 2001, Fajans et al 2001, Ban et al 2002, Stanojevic et al 2004, Fernandez-Zapico et al 2009). The transcriptional regulation of calt expression in S. aurata does not necessarily apply to human ALT1.…”

Section: Discussionmentioning

confidence: 99%

Transactivation of cytosolic alanine aminotransferase gene promoter by p300 and c-Myb

Anemaet

González²,

Salgado³

et al. 2010

Journal of Molecular Endocrinology

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Alanine aminotransferase (Alt) provides a molecular link between carbohydrate and amino acid metabolism. In the cell context, the predominant Alt isozyme is located in the cytosol. To gain insight into the transcriptional regulation of the cytosolic alt gene (calt), we cloned and characterized the calt promoter from gilthead sea bream (Sparus aurata). Transient transfection of sea bass larvae cells with deleted calt promoter constructs and electrophoretic mobility shift assays allowed us to identify p300 and c-Myb as new factors in the transcriptional regulation of calt expression. Transfection studies carried out with an acetylase-deficient mutant p300 (p300DY) revealed that the acetyltransferase activity of p300 is essential for the p300-mediated transcriptional activation of S. aurata calt. We had previously found up-regulation of liver cAlt2, an alternatively spliced isoform of calt, under gluconeogenic conditions and in streptozotocin (STZ)-treated S. aurata. Quantitative RT-PCR assays showed that increased p300 and c-Myb mRNA levels in the liver of starved S. aurata contribute to enhancing the transcription of cAlt2. Consistently, the administration of insulin decreased both p300 and c-Myb expression. The mRNA levels of p300 and c-Myb were also analyzed in the liver of STZ-induced diabetic S. aurata. Treatment with STZ increased the expression of p300, whereas it decreased c-Myb. Our findings suggest an involvement of p300 and c-Myb in up-regulation of cAlt2 in the liver of S. aurata under starvation. In addition, these results provide evidence for a role of p300 in diabetes.

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Hepatocyte Nuclear Factor-1α Recruits the Transcriptional Co-Activator p300 on the GLUT2 Gene Promoter

Cited by 82 publications

References 30 publications

Nuclear Factor 1 Family Members Interact with Hepatocyte Nuclear Factor 1α to Synergistically Activate L-type Pyruvate Kinase Gene Transcription

Nuclear Factor 1 Family Members Interact with Hepatocyte Nuclear Factor 1α to Synergistically Activate L-type Pyruvate Kinase Gene Transcription

Identification and functional characterization of a novel mutation of hepatocyte nuclear factor-1α gene in a Korean family with MODY3

Transactivation of cytosolic alanine aminotransferase gene promoter by p300 and c-Myb

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