The mouse albumin promoter and a distal upstream site are simultaneously DNase I hypersensitive in liver chromatin and bind similar liver-abundant factors in vitro.

Liu, Jen-Kuei; Bergman, Yehudit; Zaret, Kenneth S.

doi:10.1101/gad.2.5.528

Cited by 71 publications

(61 citation statements)

References 73 publications

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“…1). Although others have reported that these condition-dependent differences in albumin expression are transcriptionally regulated and reflect differences in the protection of several DNasesensitive sites in regulatory elements of the albumin gene (36,37), differences in albumin mRNA expression are not associated with comparable differences in C/EBP mRNA expression ( Fig. 1).…”

Section: Rala255mentioning

confidence: 84%

“…Liu et al (37) reported that at least five distinct DNasesensitive sites in the albumin enhancer element are differentially protected in RALA255-like hepatocytes grown at permissive and restrictive temperatures. Our data suggest that some of the factors that bind to these other sites may be differentially expressed in RALA255 cells cultured at the two temperatures.…”

Section: Figmentioning

confidence: 99%

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Adenovirus-mediated Transfer of CCAAT/Enhancer-binding Protein-α Identifies a Dominant Antiproliferative Role for This Isoform in Hepatocytes

Diehl

Johns

Yang

et al. 1996

Journal of Biological Chemistry

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CCAAT/enhancer-binding protein (C/EBP) isoforms are thought to be important regulators of the hepatocyte phenotype. However, the specific physiological roles of different isoforms are poorly understood because hepatocytes express multiple C/EBPs, and various isoforms have overlapping functions. To identify the functions of C/EBP␣ in mature hepatocytes, replicationdefective adenovirus vectors were used to efficiently and homogeneously overexpress the mouse C/EBP␣ gene in a SV40 virus-conditionally transformed rat hepatocyte line that can be induced to express C/EBP␤ and C/EBP␦ but that has little endogenous C/EBP␣ expression. Hepatocytes were infected with a recombinant adenovirus vector carrying the cDNA for C/EBP␣ driven by Rous sarcoma virus promoter elements (AdCEBP␣) or a similar vector carrying the Escherichia coli lacZ gene (Ad␤gal). Staining for ␤-galactosidase demonstrated an infection efficiency of 100% at a multiplicity of infection of 25 plaque-forming units/cell and persistence of foreign gene expression for at least 9 days. Cultures infected with AdCEBP␣ had 50-fold higher levels of C/EBP␣ mRNA and protein than those infected with Ad␤gal, but similar expression of C/EBP␤. Infection with AdCEBP␣ inhibited proliferation in cells expressing little C/EBP␤, even when proliferation was driven by the SV40 transforming antigen, and also blunted mitogenic induction of the c-myc proto-oncogene in nontransformed cells with high levels of C/EBP␤. Although overexpression of C/EBP␣ consistently increased C/EBP␣ DNA binding activity, it was not sufficient for albumin expression. Infection with AdCEBP␣ only increased albumin mRNA levels in nontransformed cells that also expressed relatively high levels of C/EBP␤. Thus, in hepatocytes, C/EBP␣ has a dominant antiproliferative function, but must interact with other factors to regulate hepatocyte-specific gene expression.

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Section: Rala255mentioning

confidence: 84%

Section: Figmentioning

confidence: 99%

Adenovirus-mediated Transfer of CCAAT/Enhancer-binding Protein-α Identifies a Dominant Antiproliferative Role for This Isoform in Hepatocytes

Diehl

Johns

Yang

et al. 1996

Journal of Biological Chemistry

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“…We previously showed that when H2.35 cells are shifted from a plastic to a collagen gel substratum, they exhibit a dramatic induction of serum albumin mRNA expression. 7 Albumin mRNA is transcribed solely in the liver, [58][59][60] so it serves as a classic marker of hepatocyte differentiation. Indeed, albumin mRNA and other liverspecific products decline markedly when hepatocytes are isolated from the liver and cultured on a plastic substratum, whereas albumin and other liver-specific mRNAs continue to be expressed at high levels when primary hepatocytes are cultured on collagen ECM gels.…”

Section: Deficient Albumin Mrna Expression In the ␣ 3 -Deficient Cellmentioning

confidence: 99%

?3?1-integrin as a critical mediator of the hepatic differentiation response to the extracellular matrix

et al. 1998

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The extracellular matrix (ECM) promotes the differentiation of many cell types, and ECM remodeling in the liver has been implicated in embryonic development, tissue injury, and oncogenesis. Integrins are heterodimeric ECM receptors that play critical roles in transducing the composition of the ECM in the cell environment. We previously showed that mouse H2.35 cells, a conditionally transformed, liver-derived cell line, assume a more differentiated hepatocyte morphology and enhanced liver-specific gene expression when the cells are cultured on gelatinous ECM substrata. Here we show that H2.35 cells express relatively high levels of ␣ 3 ␤ 1 -integrins, similar to that previously shown for immature hepatocytes, transformed hepatocytes, and biliary cells. However, the cell morphological responses that depend on ␣ 3 ␤ 1 -integrin have not been defined. We found that transfecting H2.35 cells with antisense RNA construct directed to ␣ 3 -subunit messenger RNA perturbs the initial cell attachment to laminin and collagen, and strongly inhibits cell morphological, proliferative, and gene expression responses to a collagen gel substratum. In situ hybridization to mouse embryo tissues demonstrates the presence of ␣ 3 -subunit messenger RNAs in newly formed hepatocytes. We suggest that ␣ 3 ␤ 1 -integrins are important for immature and transformed hepatocytes to respond morphologically to the extracellular matrix. (HEPATOLOGY 1998;28:1095-1104.)Tissue-specific gene expression, morphogenesis, and cell migration are promoted by interactions between cells and the surrounding extracellular matrix (ECM). For example, early hepatocyte differentiation begins as foregut endodermal cells enter the new collagenous environment of the surrounding mesenchyme, 1 and the role of the ECM in adult hepatocyte differentiation is well established. [2][3][4][5][6][7][8] Other examples of ECMpromoted differentiation include the differentiation of keratinocytes, 9 gastrulation in Pleurodeles embryos, 10 and the epithelial conversion of kidney mesenchyme 11 (for review, see Adams and Watt 12 ). The ECM is present in all animals from the earliest stages of development and is composed of a mixture of proteins and proteoglycans such as collagens, laminin, and fibronectin. An important set of membrane receptors for ECM molecules is the integrin family of proteins. [13][14][15] Integrins are heterodimers of ␣ and ␤ subunits, with each subunit containing an N-terminal extracellular domain, a transmembrane domain, and a C-terminal intracellular domain. Integrins activate common as well as subgroupspecific intracellular signaling pathways in response to the ECM. 16,17 Membrane proximal events triggered by integrin ligation include the activation of the focal adhesion kinase 18 by the ␤ subunit and the recruitment of adapter protein Shc by certain ␣ subunits within heterodimers. 19 More ␣ subunits are known than ␤ subunits, and the particular combination of ␣ and ␤ partners determines the ligand specificity for ECM molecules. An ECM protein can be recognized...

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“…DNase I Hypersensitivity Assays-The basic protocol has been described (40), and all preparatory steps were carried out at 4°C. Briefly, 1.5 to 2 ϫ 10 8 trypsinized cells were centrifuged at 2000 rpm for 10 min.…”

Section: Cells-a Set Of Matched P53mentioning

confidence: 99%

Constitutive DNase I Hypersensitivity of p53-Regulated Promoters

Braastad

Han

Hendrickson

2003

Journal of Biological Chemistry

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The ability of p53 to alter, at the transcriptional level, the gene expression of downstream targets is critical for its role as a tumor suppressor. Most models of p53 activation postulate the stepwise recruitment by p53 of coactivators, histone acetyltransferases, and/or chromatin remodeling factors to a promoter region to facilitate the subsequent access of the general transcriptional machinery required for transcriptional induction. We demonstrate here, however, that the promoter regions for the p53 target genes, p21, 14-3-3, and KARP-1, exist in a constitutively open conformation that is readily accessible to DNase I. This conformation was not altered by DNA damage or by whether p53 was present or absent in the cell. In contrast, p53 response elements, which resided outside the immediate promoter regions, existed within DNase I-resistant chromatin domains. Thus, p53 activation of downstream target genes occurs without p53 inducing chromatin alterations detectable by DNase I accessibility at either the promoter or the response element. As such, these data support models of p53 activation that do not require extensive chromatin alterations to support cognate gene expression.The differential chromatin structure and nuclease accessibility at a promoter region has long been recognized as a key distinguishing feature between active and inactive genes (reviewed in Ref. 1). Almost invariably, the promoter regions of active genes are marked experimentally by hypersensitivity to restriction endonucleases (2, 3) or, more commonly, DNase I (4). Although this hypersensitivity can be caused by torsional or topological stress in the DNA and distortions in the chromatin structure resulting from transcription factor binding, it is generally caused by the absence of nucleosomes or their remodeling (1, 4). The paucity of nucleosomes, in turn, is a direct consequence of the repressive effect that nucleosomes have on the transcriptional machinery and the requirement to alleviate that effect for productive transcription to occur (5-7). Thus, inactive genes usually have promoters that are nucleosomal, are insensitive to DNase I, and are regarded as being in a closed confirmation whereas active genes usually have core promoters that are nucleosome-free, hypersensitive to DNase I, and in an open configuration. Consequently, one of the hallmarks of gene induction mechanisms is the remodeling of the nucleosomal architecture of a promoter as it is activated (5, 6, 8).Enormous strides have been made in the last decade in understanding transcriptional activation at the chromatin level. In particular, the activation of expression of many, although not all (9 -11), inducible eukaryotic genes is consistent with what can collectively be called recruitment models of gene activation (3, 7, 8) (reviewed in Ref. 12). These models usually require, in response to some extracellular cue, the induction of a specific transcription factor and the subsequent interaction of that factor with its cognate response element, which is invariably a cis-acting ...

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The mouse albumin promoter and a distal upstream site are simultaneously DNase I hypersensitive in liver chromatin and bind similar liver-abundant factors in vitro.

Cited by 71 publications

References 73 publications

Adenovirus-mediated Transfer of CCAAT/Enhancer-binding Protein-α Identifies a Dominant Antiproliferative Role for This Isoform in Hepatocytes

Adenovirus-mediated Transfer of CCAAT/Enhancer-binding Protein-α Identifies a Dominant Antiproliferative Role for This Isoform in Hepatocytes

?3?1-integrin as a critical mediator of the hepatic differentiation response to the extracellular matrix

Constitutive DNase I Hypersensitivity of p53-Regulated Promoters

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