scholarly journals Hepatocyte Nuclear Factor 4α (HNF4α) Is a Transcription Factor of Vertebrate Fatty Acyl Desaturase Gene as Identified in Marine Teleost Siganus canaliculatus

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0160361 ◽  
Author(s):  
Yewei Dong ◽  
Shuqi Wang ◽  
Junliang Chen ◽  
Qinghao Zhang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Acyl ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Marine Teleost ◽  
Desaturase Gene ◽  
Siganus Canaliculatus ◽  
Hepatocyte Nuclear Factor 4Α ◽  
Fatty Acyl Desaturase

scholarly journals Hnf4α Is Involved in LC-PUFA Biosynthesis by Up-Regulating Gene Transcription of Elongase in Marine Teleost Siganus canaliculatus

2018 ◽  
Vol 19 (10) ◽  
pp. 3193 ◽  
Author(s):  
Yuanyou Li ◽  
Xiaowei Zeng ◽  
Yewei Dong ◽  
Cuiying Chen ◽  
Cuihong You ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Fatty Acyl ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Marine Teleost ◽  
Siganus Canaliculatus ◽  
Pufa Biosynthesis ◽  
Hepatocyte Nuclear Factor 4Α ◽  
Rabbitfish Siganus Canaliculatus

The rabbitfish Siganus canaliculatus is the first marine teleost shown to be able to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors catalyzed by two fatty acyl desaturases (fad) including Δ4 Fad and Δ6/Δ5 Fad as well as two elongases (Elovl4 and Elovl5). Previously, hepatocyte nuclear factor 4α (Hnf4α) was demonstrated to be predominant in the transcriptional regulation of two fads. To clarify the regulatory mechanisms involved in rabbitfish lipogenesis, the present study focused on the regulatory role of Hnf4α to elovl5 expression and LC-PUFA biosynthesis. Bioinformatics analysis predicted two potential Hnf4α elements in elovl5 promoter, one binding site was confirmed to interact with Hnf4α by gel shift assays. Moreover, overexpression of hnf4α caused a remarkable increase both in elovl5 promoter activity and mRNA contents, while knock-down of hnf4α in S. canaliculatus hepatocyte line (SCHL) resulted in a significant decrease of elovl5 gene expression. Meanwhile, hnf4α overexpression enhanced LC-PUFA biosynthesis in SCHL cell, and intraperitoneal injection to rabbitfish juveniles with Hnf4α agonists (Alverine and Benfluorex) increased the expression of hnf4α, elvol5 and Δ4 fad, coupled with an increased proportion of total LC-PUFA in liver. The results demonstrated that Hnf4α is involved in LC-PUFA biosynthesis by up-regulating the transcription of the elovl5 gene in rabbitfish, which is the first report of Hnf4α as a transcription factor of the elovl5 gene in vertebrates.

scholarly journals Maturity-Onset Diabetes of the Young Type 1 (MODY1)-Associated Mutations R154X and E276Q in Hepatocyte Nuclear Factor 4α (HNF4α) Gene Impair Recruitment of p300, a Key Transcriptional Coactivator

2001 ◽  
Vol 15 (7) ◽  
pp. 1200-1210 ◽  
Author(s):  
Jérôme Eeckhoute ◽  
Pierre Formstecher ◽  
Bernard Laine
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activity ◽  
Cell Function ◽  
Nuclear Factor ◽  
Maturity Onset Diabetes ◽  
Hepatocyte Nuclear Factor ◽  
Β Cell ◽  
Β Cell Function ◽  
Hepatocyte Nuclear Factor 4Α

Abstract Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor involved in glucose homeostasis and is required for normal β-cell function. Mutations in the HNF4α gene are associated with maturity-onset diabetes of the young type 1. E276Q and R154X mutations were previously shown to impair intrinsic transcriptional activity (without exogenously supplied coactivators) of HNF4α. Given that transcriptional partners of HNF4α modulate its intrinsic transcriptional activity and play crucial roles in HNF4α function, we investigated the effects of these mutations on potentiation of HNF4α activity by p300, a key coactivator for HNF4α. We show here that loss of HNF4α function by both mutations is increased through impaired physical interaction and functional cooperation between HNF4α and p300. Impairment of p300-mediated potentiation of HNF4α transcriptional activity is of particular importance for the E276Q mutant since its intrinsic transcriptional activity is moderately affected. Together with previous results obtained with chicken ovalbumin upstream promoter-transcription factor II, our results highlight that impairment of recruitment of transcriptional partners represents an important mechanism leading to abnormal HNF4α function resulting from the MODY1 E276Q mutation. The impaired potentiations of HNF4α activity were observed on the promoter of HNF1α, a transcription factor involved in a transcriptional network and required for β-cell function. Given its involvement in a regulatory signaling cascade, loss of HNF4α function may cause reduced β-cell function secondary to defective HNF1α expression. Our results also shed light on a better structure-function relationship of HNF4α and on p300 sequences involved in the interaction with HNF4α.

scholarly journals Quantitative Proteomics Identifies DNA Repair as a Novel Biological Function for Hepatocyte Nuclear Factor 4α in Colorectal Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 626 ◽  
Author(s):  
Jean-Philippe Babeu ◽  
Samuel D. Wilson ◽  
Élie Lambert ◽  
Dominique Lévesque ◽  
François-Michel Boisvert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Quantitative Proteomics ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Colorectal Cancer Cells ◽  
Hepatocyte Nuclear Factor 4Α

Hepatocyte nuclear factor 4α (HNF4α) is a transcription factor that acts as a master regulator of genes for several endoderm-derived tissues, including the intestine, in which it plays a central role during development and tumorigenesis. To better define the mechanisms by which HNF4α can influence these processes, we identified proteins interacting with HNF4α using stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomics with either immunoprecipitation of green fluorescent protein (GFP) or with proximity-dependent purification by the biotin ligase BirA (BioID), both fused to HNF4α. Surprisingly, these analyses identified a significant enrichment of proteins characterized with a role in DNA repair, a so far unidentified biological feature of this transcription factor. Several of these proteins including PARP1, RAD50, and DNA-PKcs were confirmed to interact with HNF4α in colorectal cancer cell lines. Following DNA damage, HNF4α was able to increase cell viability in colorectal cancer cells. Overall, these observations identify a potential role for this transcription factor during the DNA damage response.

scholarly journals Proteomics Reveals a Physical and Functional Link between Hepatocyte Nuclear Factor 4α and Transcription Factor IID

2009 ◽  
Vol 284 (47) ◽  
pp. 32405-32412 ◽  
Author(s):  
Hidehisa Takahashi ◽  
Skylar Martin-Brown ◽  
Michael P. Washburn ◽  
Laurence Florens ◽  
Joan W. Conaway ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Functional Link ◽  
Hepatocyte Nuclear Factor 4Α ◽  
Transcription Factor Iid
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