Transcription factor

About: Transcription factor is a research topic. Over the lifetime, 82881 publications have been published within this topic receiving 5400448 citations. The topic is also known as: transcription factors.

mdm2 expression is induced by wild type p53 activity.

Abstract: We have recently characterized a 95 kDa protein, p95, which exhibits enhanced binding to temperature-sensitive p53 (ts-p53) when cells are shifted down to 325 degrees C, a temperature at which ts-p53 possesses wild-type (wt)-like activities In the present study we show that p95 is a product of the mdm2 putative proto-oncogene The enhanced complex formation of mdm2 with ts-p53 in cells maintained at 325 degrees C is due to an elevation in total mdm2 protein levels following the temperature shift We further demonstrate that the induction of mdm2 expression by t p53 activity is at the mRNA level The induction occurs with very rapid kinetics and does not require de novo protein synthesis, suggesting a direct involvement of p53 in the process Based on these data and on recent findings implicating p53 as a transcription factor, we suggest that the mdm2 gene is a target for activation by wt p53 In view of the ability of mdm2 to act as a specific antagonist of p53 activity, this induction process may serve to tightly autoregulate p53 activity in living cells

CCAAT/enhancer-binding proteins: structure, function and regulation

Abstract: CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that all contain a highly conserved, basic-leucine zipper domain at the C-terminus that is involved in dimerization and DNA binding. At least six members of the family have been isolated and characterized to date (C/EBPa–C/EBPz), with further diversity produced by the generation of different sized polypeptides, predominantly by differential use of translation initiation sites, and extensive protein–protein interactions both within the family and with other transcription factors. The function of the C/EBPs has recently been investigated by a number of approaches, including studies on mice that lack specific members, and has identified pivotal roles of the family in the control of cellular proliferation and differentiation, metabolism, inflammation and numerous other responses, particularly in hepatocytes, adipocytes and haematopoietic cells. The expression of the C/EBPs is regulated at multiple levels during several physiological and pathophysiological conditions through the action of a range of factors, including hormones, mitogens, cytokines, nutrients and certain toxins. The mechanisms through which the C/EBP members are regulated during such conditions have also been the focus of several recent studies and have revealed an immense complexity with the potential existence of cell/tissue- and species-specific differences. This review deals with the structure, biological function and the regulation of the C/EBP family.

Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes

Abstract: The synthesis of fatty acids and cholesterol, the building blocks of membranes, is regulated by three membrane-bound transcription factors: sterol regulatory element-binding proteins (SREBP)-1a, -1c, and -2. Their function in liver has been characterized in transgenic mice that overexpress each SREBP isoform and in mice that lack all three nuclear SREBPs as a result of gene knockout of SREBP cleavage-activating protein (SCAP), a protein required for nuclear localization of SREBPs. Here, we use oligonucleotide arrays hybridized with RNA from livers of three lines of mice (transgenic for SREBP-1a, transgenic for SREBP-2, and knockout for SCAP) to identify genes that are likely to be direct targets of SREBPs in liver. A total of 1,003 genes showed statistically significant increased expression in livers of transgenic SREBP-1a mice, 505 increased in livers of transgenic SREBP-2 mice, and 343 showed decreased expression in Scap–/– livers. A subset of 33 genes met the stringent combinatorial criteria of induction in both SREBP transgenics and decreased expression in SCAP-deficient mice. Of these 33 genes, 13 were previously identified as direct targets of SREBP action. Of the remaining 20 genes, 13 encode enzymes or carrier proteins involved in cholesterol metabolism, 3 participate in fatty acid metabolism, and 4 have no known connection to lipid metabolism. Through application of stringent combinatorial criteria, the transgenic/knockout approach allows identification of genes whose activities are likely to be controlled directly by one family of transcription factors, in this case the SREBPs.

Control of Pancreas and Liver Gene Expression by HNF Transcription Factors

Abstract: The transcriptional regulatory networks that specify and maintain human tissue diversity are largely uncharted. To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1α, HNF4α, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets. We identified tissue-specific regulatory circuits formed by HNF1α, HNF4α, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. Our results suggest how misregulation of HNF4α can contribute to type 2 diabetes.