Liver-Enriched Transcription Factors in Liver Function and Development. Part I: The Hepatocyte Nuclear Factor Network and Liver-Specific Gene Expression

2002 ◽  
Vol 54 (1) ◽  
pp. 129-158 ◽  
Author(s):  
H. Schrem
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Liver Function ◽  
Specific Gene ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Specific Gene Expression

scholarly journals Hepatocyte Nuclear Factor 3β (Foxa2) Is Dispensable for Maintaining the Differentiated State of the Adult Hepatocyte

2000 ◽  
Vol 20 (14) ◽  
pp. 5175-5183 ◽  
Author(s):  
Newman J. Sund ◽  
Siew-Lan Ang ◽  
Sara Dutton Sackett ◽  
Wei Shen ◽  
Nathalie Daigle ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Liver Function ◽  
Critical Role ◽  
Normal Liver ◽  
Specific Gene ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Normal Liver Function ◽  
Adult Mice

ABSTRACT Liver-specific gene expression is controlled by a heterogeneous group of hepatocyte-enriched transcription factors. One of these, the winged helix transcription factor hepatocyte nuclear factor 3β (HNF3β or Foxa2) is essential for multiple stages of embryonic development. Recently, HNF3β has been shown to be an important regulator of other hepatocyte-enriched transcription factors as well as the expression of liver-specific structural genes. We have addressed the role of HNF3β in maintenance of the hepatocyte phenotype by inactivation ofHNF3β in the liver. Remarkably, adult mice lackingHNF3β expression specifically in hepatocytes are viable, with histologically normal livers and normal liver function. Moreover, analysis of >8,000 mRNAs by array hybridization revealed that lack ofHNF3β affects the expression of only very few genes. Based on earlier work it appears that HNF3β plays a critical role in early liver development; however, our studies demonstrate that HNF3β is not required for maintenance of the adult hepatocyte or for normal liver function. This is the first example of such functional dichotomy for a tissue specification transcription factor.

Transcription Factors Controlling Muscle-Specific Gene Expression

1993 ◽  
pp. 93-115 ◽  
Author(s):  
John J. Schwarz ◽  
James F. Martin ◽  
Eric N. Olson
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Specific Gene ◽  
Specific Gene Expression

scholarly journals Inhibition of hepatocyte nuclear factor 4 transcriptional activity by the nuclear factor κB pathway

2006 ◽  
Vol 398 (3) ◽  
pp. 439-450 ◽  
Author(s):  
Varvara Nikolaidou-Neokosmidou ◽  
Vassilis I. Zannis ◽  
Dimitris Kardassis
Keyword(s):  
Gene Expression ◽  
Inflammatory Cytokine ◽  
Transcriptional Activity ◽  
Binding Protein ◽  
Nuclear Factor Κb ◽  
Specific Gene ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Response Element ◽  
Hepatocyte Nuclear Factor 4

HNF-4 (hepatocyte nuclear factor 4) is a key regulator of liver-specific gene expression in mammals. We have shown previously that the activity of the human APOC3 (apolipoprotein C-III) promoter is positively regulated by the anti-inflammatory cytokine TGFβ (transforming growth factor β) and its effectors Smad3 (similar to mothers against decapentaplegic 3) and Smad4 proteins via physical and functional interactions between Smads and HNF-4. We now show that the pro-inflammatory cytokine TNFα (tumour necrosis factor α) antagonizes TGFβ for the regulation of APOC3 gene expression in hepatocytes. TNFα was a strong inhibitor of the activity of apolipoprotein promoters that harbour HNF-4 binding sites and this inhibition required HNF-4. Using specific inhibitors of TNFα-induced signalling pathways, it was shown that inhibition of the APOC3 promoter by TNFα involved NF-κB (nuclear factor κB). Latent membrane protein 1 of the Epstein–Barr virus, which is an established potent activator of NF-κB as well as wild-type forms of various NF-κB signalling mediators, also inhibited strongly the APOC3 promoter and the transactivation function of HNF-4. TNFα had no effect on the stability or the nuclear localization of HNF-4 in HepG2 cells, but inhibited the binding of HNF-4 to the proximal APOC3 HRE (hormone response element). Using the yeast-transactivator-GAL4 system, we showed that both AF-1 and AF-2 (activation functions 1 and 2) of HNF-4 are inhibited by TNFα and that this inhibition was abolished by overexpression of different HNF-4 co-activators, including PGC-1 (peroxisome-proliferator-activated-receptor-γ co-activator 1), CBP [CREB (cAMP-response-element-binding protein) binding protein] and SRC3 (steroid receptor co-activator 3). In summary, our findings indicate that TNFα, or other factors that trigger an NF-κB response in hepatic cells, inhibit the transcriptional activity of the APOC3 and other HNF-4-dependent promoters and that this inhibition could be accounted for by a decrease in DNA binding and the down-regulation of the transactivation potential of the AF-1 and AF-2 domains of HNF-4.

scholarly journals The Developmental Control of Osteoblast-Specific Gene Expression: Role of Specific Transcription Factors and the Extracellular Matrix Environment

1999 ◽  
Vol 10 (1) ◽  
pp. 40-57 ◽  
Author(s):  
R.T. Franceschi
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Developmental Process ◽  
Positional Information ◽  
Cleidocranial Dysplasia ◽  
Specific Gene ◽  
Tissue Specific ◽  
Specific Gene Expression ◽  
Specific Differentiation

Bone formation is a carefully controlled developmental process involving morphogen-mediated patterning signals that define areas of initial mesenchyme condensation followed by induction of cell-specific differentiation programs to produce chondrocytes and osteoblasts. Positional information is conveyed via gradients of molecules, such as Sonic Hedgehog that are released from cells within a particular morphogenic field together with region-specific patterns of hox gene expression. These, in turn, regulate the localized production of bone morphogenetic proteins and related molecules which initiate chondrocyte- and osteoblast-specific differentiation programs. Differentiation requires the initial commitment of mesenchymal stem cells to a given lineage, followed by induction of tissue-specific patterns of gene expression. Considerable information about the control of osteoblast-specific gene expression has come from analysis of the promoter regions of genes encoding proteins like osteocalcin that are selectively expressed in bone. Both general and tissue-specific transcription factors control this promoter. Osf2/Cbfal, the first osteoblast-specific transcription factor to be identified, is expressed early in the osteoblast lineage and interacts with specific DNA sequences in the osteocalcin promoter essential for its selective expression in osteoblasts. The OSF2/CBFA1 gene is necessary for the development of mineralized tissues, and its mutation causes the human disease, cleidocranial dysplasia. Committed osteoprogenitor cells already expressing Osf2/Cbfa1 must synthesize a collagenous ECM before they will differentiate. A ceII:ECM interaction mediated by integrin-type cell-surface receptors is essential for the induction of osteocalcin and other osteoblast-related proteins. This interaction stimulates the binding of Osf2/Cbfa 1 to the osteocalcin promoter through an as-yet-undefined mechanism.

scholarly journals Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors

2002 ◽  
Vol 21 (19) ◽  
pp. 5225-5234 ◽  
Author(s):  
Xun Wang ◽  
John D. Crispino ◽  
Danielle L. Letting ◽  
Minako Nakazawa ◽  
Mortimer Poncz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Specific Gene ◽  
Ets Transcription Factors ◽  
Specific Gene Expression
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