Involvement of transcription factor C/EBP-beta in stimulation of PEPCK gene expression during exercise

1996 ◽  
Vol 270 (5) ◽  
pp. R1005-R1012 ◽  
Author(s):  
S. E. Nizielski ◽  
C. Arizmendi ◽  
A. R. Shteyngarts ◽  
C. J. Farrell ◽  
J. E. Friedman
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Transcription ◽  
Dna Sequences ◽  
Prolonged Exercise ◽  
Nuclear Proteins ◽  
Control Of Gene Expression ◽  
Total Binding ◽  
Factor C ◽  
Stimulation Of

Prolonged exercise increases gluconeogenesis and activates transcription of the hepatic phosphoenol pyruvate carboxykinase (PEPCK) gene. The mechanisms that regulate the transcriptional control of gene expression depend on the interaction of nuclear proteins with distinct DNA sequences. To determine the involvement with the liver-enriched transcription factor CCAAT/enhancer binding protein beta (C/EMP-beta) in the induction of PEPCK gene transcription during prolonged exercise or adenosine 3',5'-cyclic monophosphate (cAMP) treatment, we examined C/EBP-beta mRNA and nuclear protein concentrations, as well as C/EBP-beta binding to the PEPCK promoter at the cAMP response element (CRE)(-87/-74) and P3I (-248/-230) binding sites. The requirement of these DNA elements for exercise-induced stimulation of PEPCK gene expression was established in transgenic mice carrying -460 +/- 73 of the PEPCK promoter with a mutation in either the CRE or P3I binding domain linked to a bovine growth hormone (bGH) reporter gene. In mice carrying the intact promoter, prolonged exercise increased the concentration of liver bGH mRNA by 510% compared with an increase of only 270% in mice with a mutation in either the CRE or P3I site. Exercise or cAMP injection induced a 7.5- and 13-fold increase in nuclear C/EBP-beta protein, respectively. In electrophoretic mobility shift assays (EMSA), the total quantity of nuclear proteins bound to either oligomer was not altered by treatment. However, addition of C/EBP-beta antisera in the EMSA in a supershift assay indicated that liver nuclear extracts from exercised or cAMP-treated mice demonstrated significantly greater DNA binding due to C/EBP-beta (CRE: control 44.4 +/- 2.3%, exercise 56.7% +/- 2.2%, cAMP 54.5 +/- 3.6% of total binding, P < 0.001; P3I: control 35.8 +/- 2.5%, exercise 64.9 +/- 1.9%, cAMP 57.3 +/- 2.5% of total binding, P < 0.001). Taken together, these results suggest that exercise and cAMP treatment induce a transient increase in C/EBP-beta that may contribute to the molecular mechanism for signaling PEPCK gene transcription and increasing gluconeogenesis during exercise.

scholarly journals Role of polycomb repressive complex 2 in regulation of human transcription factor gene expression

2021 ◽  
Author(s):  
Jay Brown
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Dna Sequences ◽  
Binding Sites ◽  
Regulatory Control ◽  
Polycomb Repressive Complex ◽  
Control Of Gene Expression ◽  
Polycomb Repressive Complex 2

Control of gene expression is now recognized as a central issue in the field of molecular biology. We now know the sequences of many genomes including that of the human genome, and we know the nature of many pathways involved in control of gene expression. It remains difficult, however, to look at the DNA sequences surrounding a particular gene and tell which methods of regulatory control are in use. I have been pursuing the idea that progress might be made by comparing the regulatory regions of paired gene populations in which one population is strongly expressed and the other weakly. Here I report the results obtained with human genes encoding transcription factors (TF). In this population, broadly expressed genes are strongly expressed while tissue targeted TF expression is suppressed in most tissues. The results demonstrated that the promoter region of broadly expressed TF genes is enriched in binding sites for POLR2A, a component of RNA polymerase II while promoters of tissue targeted genes are enriched in EZH2, a subunit of polycomb repressive complex 2 (PRC2). It was rare to observe promoters with binding sites for both POLR2A and EZH2. The findings are interpreted to indicate that strong expression of broadly expressed TF genes is due to the presence of RNA polymerase II at the promoter while weak expression of tissue targeted promoters results from the presence of PRC2. Finally, transcription factor families were compared in the proportion of broadly expressed and tissue targeted genes they contain. The results demonstrated that most families possess both broadly expressed and tissue targeted members. For instance, this was the case with 16 of 20 TF families examined. The results are interpreted to indicate that while individual TFs such as EZH2 may be specific for broadly expressed or tissue targeted genes, this is not a property of most TF families.

scholarly journals The AML-associated K313 mutation enhances C/EBPα activity by leading to C/EBPα overexpression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ian Edward Gentle ◽  
Isabel Moelter ◽  
Mohamed Tarek Badr ◽  
Konstanze Döhner ◽  
Michael Lübbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activity ◽  
Target Gene ◽  
Wild Type ◽  
Elevated Expression ◽  
Factor C ◽  
Acute Myeloid

AbstractMutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.

scholarly journals Signal Transducer and Activator of Transcription (Stat) 5b-Mediated Inhibition of Insulin-Like Growth Factor Binding Protein-1 Gene Transcription: A Mechanism for Repression of Gene Expression by Growth Hormone

2007 ◽  
Vol 21 (6) ◽  
pp. 1443-1457 ◽  
Author(s):  
Mitsuru Ono ◽  
Dennis J. Chia ◽  
Roxana Merino-Martinez ◽  
Amilcar Flores-Morales ◽  
Terry G. Unterman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Transcription ◽  
Binding Protein ◽  
Critical Role ◽  
Somatic Growth ◽  
Transcript Profiling ◽  
Signal Transducer ◽  
Igf Binding ◽  
Igf Binding Protein

Abstract GH plays a central role in controlling somatic growth, tissue regeneration, and intermediary metabolism in most vertebrate species through mechanisms dependent on the regulation of gene expression. Recent studies using transcript profiling have identified large cohorts of genes whose expression is induced by GH. Other results have demonstrated that signal transducer and activator of transcription (Stat) 5b, a latent transcription factor activated by the GH receptor-associated protein kinase, Jak2, is a key agent in the GH-stimulated gene activation that leads to somatic growth. By contrast, little is known about the steps through which GH-initiated signaling pathways reduce gene expression. Here we show that Stat5b plays a critical role in the GH-regulated inhibition of IGF binding protein-1 gene transcription by impairing the actions of the FoxO1 transcription factor on the IGF binding protein-1 promoter. Additional observations using transcript profiling in the liver indicate that Stat5b may be a general mediator of GH-initiated gene repression. Our results provide a model for understanding how GH may simultaneously stimulate and inhibit the expression of different cohorts of genes via the same transcription factor, potentially explaining how GH action leads to integrated biological responses in the whole organism.

Role of heat shock transcription factor in yeast metallothionein gene expression

1991 ◽  
Vol 11 (7) ◽  
pp. 3676-3681
Author(s):  
W M Yang ◽  
W Gahl ◽  
D Hamer
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Heat Shock ◽  
Gene Transcription ◽  
Heat Shock Factor ◽  
Heat Shock Transcription Factor ◽  
Wild Type ◽  
Promoter Sequences ◽  
Metallothionein Gene ◽  
Upstream Promoter

The induction of Saccharomyces cerevisiae metallothionein gene transcription by Cu and Ag is mediated by the ACE1 transcription factor. In an effort to detect additional stimuli and factors that regulate metallothionein gene transcription, we isolated a Cu-resistant suppressor mutant of an ACE1 deletion strain. Even in the absence of metals, the suppressor mutant exhibited high basal levels of metallothionein gene transcription that required upstream promoter sequences. The suppressor gene was cloned, and its predicted product was shown to correspond to yeast heat shock transcription factor with a single-amino-acid substitution in the DNA-binding domain. The mutant heat shock factor bound strongly to metallothionein gene upstream promoter sequences, whereas wild-type heat shock factor interacted weakly with the same region. Heat treatment led to a slight but reproducible induction of metallothionein gene expression in both wild-type and suppressor strains, and Cd induced transcription in the mutant strain. These studies provide evidence for multiple pathways of metallothionein gene transcriptional regulation in S. cerevisiae.

Epigenetic Control of C/EBPa by Noncoding RNAs.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3644-3644
Author(s):  
Annalisa Di Ruscio ◽  
Alexander K Ebralidze ◽  
Francesco D'Alò ◽  
Maria Teresa Voso ◽  
Giuseppe Leone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Gene Locus ◽  
Conflicts Of Interest ◽  
Lentiviral Vector ◽  
Rt Pcr ◽  
Hematopoietic Stem ◽  
Factor C

Abstract Abstract 3644 Poster Board III-580 Little is currently known about the role of noncoding RNA transcripts (ncRNA) in gene regulation; although most, and perhaps all, gene loci express such transcripts. Our previous results with the PU.1 gene locus showed a shared transcription factor complex and chromatin configuration requirements for biogenesis of both messenger and ncRNAs. These ncRNAs were localized within the nuclear and cytoplasmic compartments. Disrupting ncRNAs in the cytoplasmic cellular fraction results in increased PU.1 mRNA and protein. Recently, we have focused on the C/EBPa gene locus and observed extensive noncoding transcription. The transcription factor C/EBPa plays a pivotal role in hematopoietic stem cell (HSC) commitment and differentiation. Expression of the C/EBPa gene is tightly regulated during normal hematopoietic development, and dysregulation of C/EBPa expression can lead to lung cancer and leukemia. However, little is known about how the C/EBPa gene is regulated in vivo. In this study, we characterize ncRNAs derived from the C/EBPa locus and demonstrate their functional role in regulation of C/EBPa gene expression. First, northern blot analysis and RT PCR determined a predominantly nuclear localization of the C/EBPa ncRNAs. Second, strand-specific quantitative RT PCR demonstrated a concordant expression of coding and noncoding C/EBPa transcripts. Next, we investigated the results of ablation of ncRNAs using a lentiviral vector containing ncRNA-targeting shRNAs on the expression of the C/EBPa gene. We have observed that reduced levels of ncRNAs leads to a significant downregulation of the expression of coding messenger RNA. These data strongly suggest that C/EBPa ncRNAs play an important role in maintaining optimal expression of the C/EBPa gene at different stages of hematopoiesis and makes targeting noncoding transcripts a novel and attractive tool in correcting aberrant gene expression levels. Disclosures: No relevant conflicts of interest to declare.

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