Tissue-specific expression is conferred by a sequence from the 5′ end of the rat albumin gene.

Ott, Marie‐Odile; Sperling, Linda; Herbomel, Philippe; Yaniv, Moshe; Weiss, Mary C.

doi:10.1002/j.1460-2075.1984.tb02164.x

Cited by 200 publications

(90 citation statements)

References 39 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transcriptional regulation in liver cell types has been mainly studied in hepatoma cell lines (Ott et al, 1984;Shaw et al, 1996) although, recently, primary hepatocytes have been shown to express promoter-reporter gene constructs (Hahn et al, 1991 ;Le Cam et al, 1994;Trottier et al, 1995) in the presence of added extracellular matrix components. Other models have been developed, such as the spheroid or sandwich methods, but they have been poorly described with regard to their potential to maintain drug metabolism capacities (Bader et al, 1994(Bader et al, , 1996Koebe et al, 1994;Niwa et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Major Detoxication Functions by Phenobarbital and 3‐Methylcholanthrene in Co‐Cultures of Rat Hepatocytes and Liver Epithelial Cells

Lerche

Fautrel

Shaw³

et al. 1997

European Journal of Biochemistry

View full text Add to dashboard Cite

In the present study, we analysed the expression of monooxygenase activities and mRNAs associated with cytochrome P-450 (CUP), including CYPlAU2, CYP2B1/2, CYP2C6, CYP2E1, CYP3A1/2, glutathione transferase a (GSTa), aldehyde dehydrogenase and epoxide hydrolase in co-cultures of primary rat hepatocytes and rat liver epithelial cells. We observed that pentoxyresorufin 0-deethylation activity was well maintained and ethoxyresorufin O-deethylation activity gradually decreased during co-culture time. In addition, we showed that phenobarbital and 3-methylcholanthrene treatments resulted in a significant increase of these activities.Two general patterns of accumulation of liver-specific mRNAs were observed. CYPl A1 /2, CYP2B1/2, CYP3All2, GSTa, aldehyde dehydrogenase and epoxide hydrolase mRNAs were maintained at a stable level, whereas CYP2C6 and CYP2E1 mRNAs showed a continuous decline. In addition, we observed a strong increase of CYPl A1/2 (13.6-fold) and GSTu (3.9-fold) mRNA expression in 3-methylcholanthrene-treated co-cultures and induction of CYP2B1/2 (19-fold), CYP2C6 (10-fold), CYP3A1/2 (1 1 .Zfold), GSTu (9-fold), aldehyde dehydrogenase (6-fold) and epoxide hydrolase (5-fold) mRNA expression in phenobarbital-treated co-cultures. Furthermore, we demonstrated that liver-specific gene expression was restricted to hepatocytes, with the notable exception of epoxide hydrolase and CYP2E1 which were expressed in both cell types during the co-culture, as shown by the selective recovery of both hepatocytes and rat liver epithelial cells.Finally, to investigate whether co-cultures could be used to study the molecular mechanisms regulating CYP transcription, we performed transfection of hepatocytes, before the establishment of the co-culture, with large CYP2B 1 (3.9 kb) or CYP2B2 (4.5 kb) promoter chloramphenicol acetyltransferase constructs or with a construct containing a 163-bp DNA sequence element reported to confer phenobarbital responsiveness. A 2-3-fold increase over the basal level of chloramphenicol acetyltransferase activity was observed in phenobarbital-treated co-cultures transfected with the phenobarbital-responsive element construct, although phenobarbital had no effect on large CYP2B1 or CYP2B2 promoter fragments.Our results demonstrate that the co-culture system provides a good tool for studying drug metabolism, and shows promise as a new tool for analysing transcriptional regulation under the influence of xenobiotics within primary hepatocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of the Major Detoxication Functions by Phenobarbital and 3‐Methylcholanthrene in Co‐Cultures of Rat Hepatocytes and Liver Epithelial Cells

Lerche

Fautrel

Shaw³

et al. 1997

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…Therefore, it is very likely that hypomethylation and hypersensitivity to DNase I interact to define regulatory regions of these genes. In this context, data concerning the albumin and AFP regulatory regions were collected by either transient expression assays (14,25,31,55) (25); (ii) the AFPII and M-1 sites are positioned in a region defined as a tissue-specific enhancer (25; A. Pollard, unpublished results); and (iii) AFPIII and M-3 are located within a region defined as a specific silencer (25). It is thus likely that these specific alterations in chromatin structure would expose cis-acting regulatory region so that trans-acting factors could then be bound (9,60).…”

Section: Methodsmentioning

confidence: 99%

Albumin and alpha-fetoprotein gene transcription in rat hepatoma cell lines is correlated with specific DNA hypomethylation and altered chromatin structure in the 5' region.

Tratner¹,

Nahon²,

Sala‐Trepat³

et al. 1987

Mol. Cell. Biol.

View full text Add to dashboard Cite

We examined DNA methylation and DNase I hypersensitivity of the a-fetoprotein (AFP) and albumin gene region in hepatoma cell lines which showed drastic differences in the level of expression of these genes. We assayed for methylation of the CCGG sequences by using the restriction enzyme isoschizomers HpaH Many studies with different experimental systems have been carried out to elucidate the role that methylation of cytosine bases and change in chromatin structure might play in the regulation of gene expression (for reviews, see references 34 and 35).Controversial results concerning the relationship between the DNA methylation pattern and gene activity have been reported showing either a good correlation (23,47) or no correlation at all (13,46,57) between undermethylation and expression of a specific gene. Various studies involving in vitro methylation of a specific regulatory region of a gene followed by its introduction into eucaryotic cells revealed that DNA methylation does affect transcription (6,17,41,42). Recent studies indicate that undermethylation of only certain critical sites located in the 5' region of genes coding for tissue-specific proteins is necessary but not sufficient for their expression (24,30,56 (48,50). Of these variants, we chose to study an

show abstract

“…Plasmid ALB-CAT, which contains the rat albumin promoter region (-390 to + lo), has been already described [5]. Plasmid TK-CAT (constructed by Ph.…”

Section: Transient Expression Vectorsmentioning

confidence: 99%

A common liver‐specific factor binds to the rat albumin and α‐foetoprotein promoters in vitro and acts as a positive trans‐acting factor in vivo

Josè-Estanyol

Poliard

Foiret

et al. 1989

European Journal of Biochemistry

View full text Add to dashboard Cite

Rat liver nuclear extracts were tested for the presence of factors which might be common to the transcriptional regulation of both the albumin and a-foetoprotein genes. Gel shift assay showed the formation of three complexes (I, I1 and 111) with the albumin probe. Two of them (I and 111) could be displaced by the a-foetoprotein promoter. Analysis of nuclear extracts from liver, kidney, spleen and brain and competition experiments using several oligonucleotides covering regions from the albumin and a-foetoprotein promoters showed that complex 111 results from the binding of the ubiquitous nuclear factor 1, while complex I1 involves a CCAAT-box-binding protein also detected in brain and spleen extracts. Complex I is formed upon binding of a liver-specific factor to a proximal element of the rat albumin promoter. This factor also binds to a similar sequence in the a-foetoprotein promoter and is closely related to the hepatocyte nuclear factor 1, as shown by competition experiments using an oligonucleotide covering its target sequence on the p-fibrinogen promoter.Transfection competition experiments indicated that, in vivo, this factor acts as a positive trans-acting element in the expression of both the rat albumin and a-foetoprotein genes.The albumin -a-foetoprotein gene system is a powerful model for gaining insight into the mechanisms which regulate the tissue-and stage-specific transcription of eucaryotic genes. The two genes, which belong to the same family [I], are both transcribed in the liver in a reciprocal manner during the course of development [2, 31. a-Foetoprotein gene transcription is high during fetal life and gradually shuts off after birth to reach almost undetectable levels during normal adult life, while the transcription of albumin gene reaches a maximum after the fetal stage and remains high throughout adult life.Considerable information has recently been obtained on the molecular mechanisms governing the expression of the albumin and a-foetoprotein genes in the liver (see [4] for review). In particular, transient expression experiments indicated that their promoter regions are involved in the specificity of expression of these genes in the liver of several species [5 -121. As this specificity of expression is probably confered by the binding of trans-acting factors to regulatory DNA regions (see [13 -151 for reviews), the identification of nuclear factors interacting with these promoters is of fundamental importance. The albumin promoter region has recently been shown to bind several proteins [16-181. Our recent study of the binding of nuclear proteins to the rat a-foetoprotein promoter indicated that a liver-specific factor and nuclear factor 1 can recognize two elements of the a-foetoprotein promoter [19]. We have now compared the binding of rat liver nuclear pro- teins to the rat albumin and a-foetoprotein promoters in order to detect common factors which may be involved in the transcriptional regulation of these genes. Such proteins may have a more general role in controlling the liver-sp...

show abstract

Tissue-specific expression is conferred by a sequence from the 5′ end of the rat albumin gene.

Cited by 200 publications

References 39 publications

Regulation of the Major Detoxication Functions by Phenobarbital and 3‐Methylcholanthrene in Co‐Cultures of Rat Hepatocytes and Liver Epithelial Cells

Regulation of the Major Detoxication Functions by Phenobarbital and 3‐Methylcholanthrene in Co‐Cultures of Rat Hepatocytes and Liver Epithelial Cells

Albumin and alpha-fetoprotein gene transcription in rat hepatoma cell lines is correlated with specific DNA hypomethylation and altered chromatin structure in the 5' region.

A common liver‐specific factor binds to the rat albumin and α‐foetoprotein promoters in vitro and acts as a positive trans‐acting factor in vivo

Contact Info

Product

Resources

About