Differential Roles of Upstream Stimulatory Factors 1 and 2 in the Transcriptional Response of Liver Genes to Glucose

Vallet, V.; Casado, Marta; Henrion, Alexandra; Bucchini, Danielle; Raymondjean, Michel; Kahn, Axel; Vaulont, Sophie

doi:10.1074/jbc.273.32.20175

Cited by 121 publications

(115 citation statements)

References 30 publications

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“…In this regard, it is striking that the transcriptional activity of USF is always altered indirectly, rather than directly by a change in the expression of the USF proteins. Together with the early embryonic lethality of the USF-null mice (Sirito et al, 1998;Vallet et al, 1998), this observation strongly suggests that, in addition to their important role in the transcriptional regulation of growth-related genes, the USF proteins may serve another function that is essential for cellular viability.…”

Section: Discussionmentioning

confidence: 99%

Loss of USF transcriptional activity in breast cancer cell lines

1999

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USF is a family of transcription factors that are structurally related to the Myc oncoproteins and also share with Myc a common DNA-binding speci®city. USF overexpression can prevent c-Myc-dependent cellular transformation and also inhibit the proliferation of certain transformed cells. These antiproliferative activities suggest that USF inactivation could be implicated in carcinogenesis. To explore this possibility, we compared the activities of the ubiquitous USF1 and USF2 proteins in several cell lines derived from either normal breast epithelium or breast tumors. The DNAbinding activities of USF1 and USF2 were present at similar levels in all cell lines. In the non-tumorigenic MCF-10A cells, USF in general, and USF2 in particular, exhibited strong transcriptional activities. In contrast, USF1 and USF2 were completely inactive in three out of six transformed breast cell lines investigated, while the other three transformed cell lines exhibited loss of USF2 activity. Analyses in cells cultured from healthy tissue con®rmed the transcriptional activity of USF in normal human mammary epithelial cells. These results demonstrate that a partial or complete loss of USF function is a common event in breast cancer cell lines, perhaps because, like Myc overexpression, it favors rapid proliferation.

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Section: Discussionmentioning

confidence: 99%

Loss of USF transcriptional activity in breast cancer cell lines

1999

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“…USF1 belongs to the basic helix-loop-helix leucine zipper family, interacts with its target DNA as a homodimer or heterodimer with USF2 and recognizes a CACGTG motif called E box in the promoter of the target genes, resulting in transcriptional activation in response to various stimuli, such as glucose and dietary carbohydrates 14,15 . Target genes of USF1 include several apolipoproteins (CIII, AII and E), hormone-sensitive lipase, fatty acid synthase, glucokinase, the glucagon receptor, ATP-binding cassette sub-family A (ABC1) member 1, and renin, making USF1 a good candidate for involvement with the central clinical features of FCHL and type 2 diabetes mellitus: glucose intolerance, hyperlipidemia, insulin resistance and hypertension.…”

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confidence: 99%

Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1)

et al. 2004

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Familial combined hyperlipidemia (FCHL), characterized by elevated levels of serum total cholesterol, triglycerides or both 1,2 , is observed in about 20% of individuals with premature coronary heart disease 1 . We previously identified a locus linked to FCHL on 1q21-q23 in Finnish families with the disease 3 . This region has also been linked to FCHL in families from other populations 4-6 as well as to type 2 diabetes mellitus 7-12 . These clinical entities have several overlapping phenotypic features, raising the possibility that the same gene may underlie the obtained linkage results. Here, we show that the human gene encoding thioredoxin interacting protein (TXNIP) on 1q, which underlies combined hyperlipidemia in mice 13 , is not associated with FCHL. We show that FCHL is linked and associated with the gene encoding upstream transcription factor 1 (USF1) in 60 extended families with FCHL, including 721 genotyped individuals (P = 0.00002), especially in males with high triglycerides (P = 0.0000009). Expression profiles in fat biopsy samples from individuals with FCHL seemed to differ depending on their carrier status for the associated USF1 haplotype. USF1 encodes a transcription factor known to regulate several genes of glucose and lipid metabolism 14-17 .To identify the gene on 1q21 associated with FCHL, we initially sequenced four functionally relevant regional candidates: TXNIP, USF1, retinoid X receptor gamma (RXRG) and apolipoprotein A-II (APOA2). In parallel, we carried out a functionally unbiased genetic analysis of 60 single-nucleotide polymorphisms (SNPs) in 26 genes in 42 families with FCHL, including the 31 families in the original linkage study 3 . We then genotyped the ten SNPs most likely to be relevant in the extended sample of 60 families of FCHL (Supplementary Table 1 online). Fifty SNPs were located in a 5.8-Mb region flanking the peak markers D1S104 and D1S1677 (Fig. 1). All the families that we studied included a proband with severe coronary heart disease and an abnormal lipid phenotype and an average of 5-6 members affected with FCHL.We sequenced the entire TXNIP gene and the 2,000-bp upstream DNA region in 60 FCHL probands. Of the 20 SNPs identified, none resulted in amino acid changes, and all were rare, with a maximal 7% allele frequency. We also did not observe the nonsense mutation causing hyperlipidemia in mice 13 . We genotyped the four most common SNPs in the 60 families with FCHL but found no evidence of association Table 2 for distances, SNP numbers and LD clusters of these SNPs). (c) The SNPs associated with triglyceride levels in men and (d) the SNPs associated with FCHL and triglycerides in all family members.

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“…These include the binding motif for activator protein 1 (AP1) which has shown to be involved in cell proliferation, differentiation and tumourigenesis, 44 upstream regulatory factor 1 (USF1) which has defined roles in regulation of genes expressed in the liver 45 and spleen focus forming virus proviral integration oncogene 1 (SPI1) which plays a role in the development of myeloid and b-lymphoid cells which are important during an immune response. 46 The functional importance of these TFs in regulation of CP expression should not be overlooked.…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of Ceruloplasmin in a South African cohort presenting with oesophageal cancer

Strickland

Matsha

Erasmus

et al. 2011

Intl Journal of Cancer

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Oesophageal cancer (OC) is a disease characterized by the development of malignant tumors in the epithelial cells lining the oesophagus. It demonstrates marked ethnic variation, with squamous cell carcinoma (SCC) being more prevalent in the Black population and adenocarcinoma (ADC) occurring more often in Caucasians. The etiology of this complex disease has been attributed to a variety of factors, including an excess of iron (resulting in increased tumourigenesis), oesophageal injury and inflammation (due in part to Barrett's oesophagus and smoking among others). The aim of this study was to determine if genetic variations identified in the ceruloplasmin (CP) gene (implicated in iron homeostasis) contribute to OC pathogenesis or susceptibility. The study cohort consisted of 96 unrelated OC patients from the Black Xhosa-speaking South African population and 88 population-matched control individuals. The promoter and coding regions of the CP gene were analyzed for DNA sequence variation using heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis, restriction fragment length polymorphism (RFLP) analysis and semi-automated bidirectional DNA sequencing analysis. Fourteen previously described and four novel variants were identified. Statistically significant associations were revealed for two of the novel variants with OC in this study and could, therefore, potentially contribute to disease susceptibility. In silico analysis of the region of the promoter spanning the identified variants sought to identify putative transcription factor binding sites (TFBSs) that could possibly regulate the expression of CP. To our knowledge, this is the first study to examine CP with respect to OC in the Black South African population.

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Differential Roles of Upstream Stimulatory Factors 1 and 2 in the Transcriptional Response of Liver Genes to Glucose

Cited by 121 publications

References 30 publications

Loss of USF transcriptional activity in breast cancer cell lines

Loss of USF transcriptional activity in breast cancer cell lines

Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1)

Molecular analysis of Ceruloplasmin in a South African cohort presenting with oesophageal cancer

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