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L E Babiss

Publications and source records attributed to L E Babiss.

At least 37 records · Page 2Linked to original sources
PubMed1990

Suppression of the progression phenotype in somatic cell hybrids occurs in the absence of altered adenovirus type 5 gene expression.

In the present study we have analyzed the genetic regulation of increased expression of transformation-associated traits, a process termed progression, in adenovirus type 5 (Ad5)-transformed secondary rat embryo cells. Somatic cell hybrids were formed between a highly progressed neomycin-resistant Ad5-transformed cloned cell line (E11-NMTneo) and an untransformed chloramphenicol-resistant rat embryo fibroblast cell line (CREFcap). Parental E11-NMTneo cells grew with high efficiency in agar, exhibited reduced 125I-epidermal growth factor (EGF) binding, and were tumorigenic in nude mice. Parental CREFcap cells exhibited phenotypes opposite to those of E11-NMTneo cells. A high proportion (84%) of the presumptive hybrid cell types obtained after fusion and genetic selection (G418 and chloramphenicol) displayed a flat morphological phenotype intermediate between CREFcap and E11-NMTneo cells, suggesting that a trans-dominant extinction phenomenon had occurred. Two hybrids with a round morphology (R), which still exhibited the progressed phenotype, and two hybrids with a flat morphology (F), which had lost the progressed phenotype, were chosen for detailed analysis. Both R hybrids grew efficiently in agar, exhibited low 125I-EGF binding, and were tumorigenic in nude mice, whereas both F hybrids grew poorly in agar, displayed increased 125I-EGF binding in comparison with E11-NMTneo and R hybrids, and were nontumorigenic in nude mice. An analysis of the viral DNA integration patterns and the rates of transcription, steady-state mRNA accumulation, and relative levels of the Ad5 E1A and E1B gene products revealed no differences among the parental and hybrid cells. These studies indicate that normal CREF cells may contain a suppressor gene(s) which can inhibit the expression of specific traits of the progression phenotype in Ad5-transformed cells and that this suppression is not associated with changes in the expression of Ad5 transforming genes.

Adenoviridae↗
PubMed1990

The mouse albumin enhancer contains a negative regulatory element that interacts with a novel DNA-binding protein.

The far-upstream mouse albumin enhancer (-10.5 to -8.43 kilobases) has both positive and negative regulatory domains which contribute to the rate and tissue specificity of albumin gene transcription. (R. S. Herbst, N. Friedman, J. E. Darnell, Jr., and L. E. Babiss, Proc. Natl. Acad. Sci. USA 86:1553-1557). In this work, the negative regulatory region has been functionally localized to sequences -8.7 to -8.43 kilobases upstream of the albumin gene cap site. In the absence of the albumin-modulating region (in which there are binding sites for the transcription factor C/EBP), the negative region can suppress a neighboring positive-acting element, thereby interfering with albumin enhancer function. The negative region is also capable of negating the positive action of the heterologous transthyretin enhancer in an orientation-independent fashion. Within this negative-acting region we can detect two DNA-binding sites, both of which are recognized by a protein present in all cell types tested. This DNA-binding activity is not competed for by any of a series of known DNA-binding sites, and hence this new protein is a candidate for a role in suppressing the albumin gene in nonhepatic cells.

Animals↗
PubMed1990

Transcriptional regulation of the albumin gene in cultured rat hepatocytes. Role of basement-membrane matrix.

The expression of tissue-specific functions by hepatocytes in primary culture is enhanced in the presence of an extracellular matrix. A basement membrane-like substratum, derived from the Engelbreth-Holm-Swarm mouse sarcoma (EHS) and termed EHS gel, supports synthesis and secretion of albumin for at least three weeks, in contrast to a conventional substratum (plastic or collagen-coated plastic), on which cells rapidly lose this function. The presence of an EHS matrix (as a substratum or added to the medium as a dilute gel) supports transcriptional activity at 30 to 35% and specific mRNA at 70 to 80% of initial values after five days of culture, at a time when transcription in cells plated in conventional culture is undetectable. For examining the cis elements required for transcriptional regulation by EHS matrix, we are utilizing recombinant adenoviruses to introduce DNA into hepatocytes, as an alternative to transfection of DNA fragments. Initial studies are presented, in which hepatocytes are cultured on either collagen-coated plastic or on EHS gel. At various times after plating, the cultures are infected with an adenovirus containing the proximal 5' regulatory region (to -441 base-pair) of the albumin gene. The results indicate no effect of EHS gel on this proximal promoter region, implying that matrix-responsive element(s) lie further upstream, possibly within the previously described enhancer at about -10,000 base-pairs.

Adenoviridae Infections↗
PubMed1989

Positive and negative regulatory elements in the mouse albumin enhancer.

Most enhancer elements so far described are comprised of multiple DNA binding sites for proteins that act to increase the rate of transcription. In this report we show that the far upstream mouse albumin enhancer element (-10.5 to -8.5 kilobase pairs) is a composite of at least three functional regions: a negative region that suppresses an otherwise positive, liver-specific enhancer element and a third region that by itself is inactive but in conjunction with the remaining elements overrides the effect of the negative region. The protein that binds to the overriding element is C/EBP, a liver-enriched transcription factor, whereas the newly identified protein that is responsible for full liver-specific enhancer activity is found in HeLa cell and spleen extracts as well as in extracts prepared from the liver. This latter protein may therefore be an example of a widely distributed protein that because of cell-specific modification or interaction has a tissue-specific, positive action on transcription.

Animals↗
PubMed1989

The cellular transcription factor E2f requires viral E1A and E4 gene products for increased DNA-binding activity and functions to stimulate adenovirus E2A gene expression.

Whereas a wide variety of cellular proteins interact with the cis-regulatory elements of the adenovirus E1A and E2A genes, only the DNA-binding activity of the cellular E2f factor is modulated by viral early-gene expression. An analysis of cellular E2f protein levels and adenovirus early-gene expression in a panel of independently cloned virus-transformed rodent cell lines and in virus-infected rodent cells has established that both the E1A 289-amino-acid (289R) protein and a yet-to-be-defined E4 gene product are required for maximal E2f DNA-binding activity. To distinguish between the multiple roles the E1A protein could serve in this process, the E2f DNA-binding activity was determined in a virus-transformed cell line which contains a conditional-lethal mutation affecting the 289R protein. Since E4 gene expression was not altered by the incubation conditions, the observation of reduced cellular E2f activity at the nonpermissive temperature suggests a direct role for the E1A 289R protein in E2f activation. When a virus containing a deletion in the E4 gene was introduced into cell lines which can complement the E4 gene defect, a correlation between high cellular E2f levels and increased rates of E2A gene transcription was observed. A time course analysis of the viral infection revealed that E2f functions catalytically to stimulate viral E2A gene transcription. These observations have led to several hypotheses concerning possible mechanisms by which elevated E2A gene expression, which leads to cytotoxicity, might be avoided in the transformed cell.

Adenovirus Early Proteins↗
PubMed1988

Regulation of adenovirus and cellular gene expression and of cellular transformation by the E1B-encoded 175-amino-acid protein.

Mutants of type 5 adenovirus that fail to express the E1B-gene-encoded 175-amino-acid (175R) protein are unable to morphologically transform primary or continuous cultures of rat embryo fibroblast cells. This phenotype could result from a direct effect of this E1B polypeptide (along with E1A polypeptides) on cellular gene expression resulting in a pathway leading to altered cell growth or from an indirect role of the 175R protein made possible by its ability to modulate viral early-gene (most likely E1A) expression. To distinguish between these two models, viruses were constructed that expressed the individual E1A 13S and 12S genes in the presence of either the E1B 175R or 495R protein. Regardless of the E1A gene product that was expressed, viruses that failed to express the E1B 175R protein were transformation defective. Additional studies suggest that the E1A 289R protein and E1B 495R protein function in a common pathway leading to the establishment of the transformed cell. We also observe that E3 gene expression by viruses that fail to express the E1A 289R protein affects the efficiency of focus formation. When tested in both nonpermissive CREF cells and permissive HeLa cells, the lack of 175R protein expression appeared to have no effect (a transient twofold decrease in E1A mRNA accumulation was observed in CREF cells) on viral early-gene expression. These results suggest that the initiation of the transformed cell phenotype occurs because of some interaction in a common pathway between the viral E1A proteins and E1B 175R protein. Furthermore, we have shown that the E1B 175R protein does not enhance the rate of transcription initiation from the mouse immunoglobulin heavy chain gene promoter when these sequences are localized on a viral genome, and it does not diminish the ability of the E1A proteins to decrease the rate of enhancer-dependent transcription.

Adenovirus Early Proteins↗
PubMed1987

Cellular promoters incorporated into the adenovirus genome. Effect of viral DNA replication on endogenous and exogenous gene transcription.

Cell-specific utilization of the albumin and immunoglobulin promoters within non-replicating adenovirus genomes has been established. With such viruses plus helper viruses we now consider the impact of infection by replicating viruses on liver-specific gene expression in hepatoma cells and of the effect of replication on the previously established limits of cell-specific expression. We find that replication of any adenovirus, whether or not it contains the albumin promoter, decreases albumin and apolipoprotein A transcription in hepatoma cells but does not affect transcription of at least four other genes expressed mainly (or only) in the liver. Thus, it may be that some hepatoma-specific genes and late adenoviral genes require a factor(s) in common, and these factors become limiting during replication. In hepatoma cells, the increased copy number of the exogenous promoters resulting from viral DNA replication did not influence the cell-specific expression noted previously; only albumin and not globin or immunoglobulin promoters in the virus were active. In contrast, replication by the same viruses in HeLa cells resulted in high levels of expression from all the exogenous promoters.

Adenoviridae↗
PubMed1987

Hepatoma variants (C2) are defective for transcriptional and post-transcriptional actions from both endogenous and viral genomes.

A series of rat hepatoma cell lines was infected with a recombinant adenovirus bearing the rat albumin promoter. Transcription from this promoter was scored directly and was highest in FAO, the differentiated parent, undetectable in C2, a cell variant that has lost almost all hepatocytic characteristics, and high again in C2-Rev7, a 'revertant' cell line derived from C2 that has regained the ability to produce many proteins characteristic of hepatocytes. The endogenous albumin gene is not transcribed in C2 cells, and at a very low rate in C2-Rev7 cells, which accumulate endogenous albumin mRNA at close to normal amounts. Thus the C2-Rev7 'recovery' of albumin mRNA concentration for the endogenous gene is based mainly on post-transcriptional events while the ability of C2-Rev7 to transcribe the albumin promoter in the viral genome is based on a transcriptional factor(s). We also showed that the C2 phenotype included post-transcriptional effects for other genes: transcription of phenylalanine hydroxylase and phosphoenolpyruvate carboxykinase mRNA sequences continue in C2 at rates equivalent to FAO but these C2 cells have no mRNA for these proteins while FAO does. In addition, C2 cells transcribed certain early adenovirus transcription units (E2 and 4) as well as FAO cells but accumulated E2 mRNAs poorly if at all. The changes that led to the C2-Rev7 cell line produced a return to normal of the ability to accumulate these viral mRNAs. Thus a major event in the C2 to C2-Rev7 transition involves post-transcriptional processes as well as the ability to transcribe the albumin promoter positioned in the virus genome.

Adenoviridae↗
PubMed1987

Mutations in the E1a gene of type 5 adenovirus result in oncogenic transformation of Fischer rat embryo cells.

Transformation of a specific clone of Fischer rat embryo (CREF) cells with wild-type 5 adenovirus (Ad5) or the E1a plus E1b transforming gene regions of Ad5 results in epithelioid transformants that grow efficiently in agar but that do not induce tumors when inoculated into nude mice or syngeneic Fischer rats. In contrast, CREF cells transformed by a host-range Ad5 mutant, H5hrl, which contains a single base-pair deletion of nucleotide 1055 in E1a resulting in a 28-kd protein (calculated) in place of the wild-type 51-kd acidic protein, display a cold-sensitive transformation phenotype and an incomplete fibroblastic morphology but surprisingly do induce tumors in nude mice and syngeneic rats. Tumors develop in both types of animals following injection of CREF cells transformed by other cold-sensitive Ad5 E1a mutants (H5dl101 and H5in106), which contain alterations in their 13S mRNA and consequently truncated 289AA proteins. CREF cells transformed with only the E1a gene (0-4.5 m.u.) from H5hrl or H5dl101 also produce tumors in these animals. To directly determine the role of the 13S E1a encoded 289AA protein and the 12S E1a encoded 243AA protein in initiating an oncogenic phenotype in adenovirus-transformed CREF cells, we generated transformed cell lines following infection with the Ad2 mutant pm975, which synthesizes the 289AA E1a protein but not the 243AA protein, and the Ad5 mutant H5dl520 and the Ad2 mutant H2dl1500, which do not produce the 289AA E1a protein but synthesize the normal 243AA E1a protein. All three types of mutant adenovirus-transformed CREF cells induced tumors in nude mice and syngeneic rats. Tumor formation by these mutant adenovirus-transformed CREF cells was not associated with changes in the arrangement of integrated adenovirus DNA or in the expression of adenovirus early genes. These results indicate, therefore, that oncogenic transformation of CREF cells can occur in the presence of a wild-type 13S E1a protein or a wild-type 12S E1a protein when either protein is present alone, but does not occur when both wild-type E1a proteins are present.

Adenoviridae↗
PubMed1987

Regulation of thyroidal inducibility of Na,K-ATPase and binding of epidermal growth factor in wild-type and cold-sensitive E1a mutant type 5 adenovirus-transformed CREF cells.

We have analyzed the relationship between expression of the transformed phenotype and thyroid hormone (triiodothyronine, T3) inducibility of Na,K-ATPase and binding of 125I-epidermal growth factor (EGF) to cell membrane receptors in wild-type (wt) and mutant type 5 adenovirus (Ad5)-transformed CREF cells displaying a cold-sensitive (cs) expression of the transformed phenotype. CREF cells respond to thyroid hormone treatment with increased Na,K-ATPase activity and bind similar levels of 125I-EGF at 32 degrees C, 37 degrees C and 39.5 degrees C. In contrast, CREF cells transformed by wt Ad5 or the E1a plus E1b-transforming genes of wt Ad5 are refractile to T3 treatment and bind lower levels of 125I-EGF than CREF cells at all three temperatures. By employing a series of cloned CREF cell lines transformed by a host-range cold-sensitive mutant virus, H5hr1 or H5dl101, or the E1a or E1a plus E1b genes from these viruses, we have investigated expression of the transformed state and its relationship with hormone inducibility and EGF binding. When cs virus, cs E1a- or cs E1a plus E1b-transformed CREF clones were grown at 32 degrees C, a nonpermissive transforming temperature in which cs-transformed cells exhibit properties similar to untransformed CREF cells, T3 induced Na,K-ATPase activity and these cells bound similar levels of 125I-EGF as CREF cells. However, when cs virus- and cs Ela plus E1b-transformed CREF clones were incubated at 37 degrees C or 39.5 degrees C, temperatures at which cs-transformed cells exhibit properties similar to wt Ad5-transformed CREF cells, they did not respond to T3 and bound lower levels of 125I-EGF than CREF cells. In the case of cs E1a-transformed CREF clones, thyroid hormone responsiveness was observed at both 32 degrees C and 37 degrees C, but not at 39.5 degrees C. By performing temperature shift experiments--i.e. 32 degrees C to 37 degrees C, 32 degrees C to 39.5 degrees C, 37 degrees C to 32 degrees C, and 39.5 degrees C to 32 degrees C, it was demonstrated that after a shift from lower to higher temperature a 24-hr lag period was required for cs-transformed CREF cells to lose T3 inducibility and exhibit reduced EGF binding, whereas 96 hr after a shift from higher to lower temperature a 96-hr lag period was required for cs-transformed cells to regain T3 inducibility and increased 125I-EGF binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoviridae↗
PubMed1987

Unique carcinogen enhancement of transformation phenotype displayed by cloned rat embryo fibroblast (CREF) cells treated with methyl methanesulfonate and infected with a specific host-range mutant of type 5 adenovirus.

Pretreatment of cloned rat embryo fibroblast (CREF) cells with methyl methanesulfonate (MMS) prior to infection with wild-type 5 adenovirus (H5wt) or a temperature-sensitive mutant of Ad5 (H5ts125) results in an MMS dose-dependent enhancement of viral transformation. With both viral isolates, MMS enhanced the transformation frequency when normalized for cell toxicity but did not induce a carcinogen dose-dependent increase in the absolute number of foci above solvent-treated controls. In contrast, pretreatment of CREF cells with MMS prior to infection with a host-range mutant of Ad5 (H5hr1) which contains a single basepair deletion in the E1a-transforming region of Ad5 and displays a cold-sensitive transformation phenotype, results in an MMS dose-dependent increase in the absolute number of transformed foci in comparison with solvent-treated controls as well as an increase in transformation frequency when normalized for cell toxicity. To explore the possible mechanism by which H5hr1 displays its unique carcinogen-enhancement of transformation (CET) phenotype we have examined the effect of MMS pretreatment on the frequency of transformation of CREF cells infected with mutants of Ad5 which were engineered to contain either a deletion (H5dl101) or an insertion (H5in106) mutation in the E1a gene region resulting in a cold-sensitive transformation phenotype similar to H5hr1. MMS-pretreated CREF cells infected with H5dl101 or H5in106 did not demonstrate a dose-dependent increase in the absolute number of transformed foci as was observed with carcinogen-pretreated H5hr1-infected CREF cells. These findings suggest that the unique CET phenotype displayed by H5hr1 may result from a second site mutation in a region of H5hr1 other than the E1a-transforming region and/or a novel interaction between gene products resulting from the specific mutation in E1a and other region(s) of the H5hr1 genome. Our investigations also indicate that the CREF/H5hr1 system should prove useful in analyzing chemical-viral interactions in cell transformation.

Adenoviridae↗
PubMed1987

Factors that interact with the rat albumin promoter are present both in hepatocytes and other cell types.

The rat albumin promoter inserted in adenovirus directs transcription in human and rodent hepatoma cells and in rodent hepatocytes (Friedman et al. 1986) and Babiss et al. (1986) but not in HeLa cells or myeloma cells. The nucleotides between -43 and -156 of the RNA start site of the rat albumin gene are required for this cell-specific expression. Protein binding studies (footprints, exonuclease III stops, and gel shifts) all indicate specific interaction in the -80 to -130 region of the gene with factors present in nuclear extracts of hepatocytes and hepatomas, but also from extracts of other cells that do not express the albumin gene. To observe albumin promoter binding, a smaller amount of extract of liver cell nuclei was required compared to extracts of HeLa cell or kidney cell nuclei. In addition, the various tests of DNA-protein interaction did not give qualitatively identical results with extracts from different cells. However, it seems clear that factors are present in several cell types where albumin genes are inactive that will bind to those DNA sequences demonstrated to be necessary for cell-specific expression of this gene. These factors could either be similar but nonidentical factors or the same factors that are modified differently in different cell types.

Animals↗
PubMed1987

Mutations in the adenovirus major late promoter: effects on viability and transcription during infection.

We developed an experimental system to examine the effects of mutations in the adenovirus major late promoter in its correct genomic location during a productive infection. A virus was constructed whose genome could be digested to give a rightward terminal DNA fragment extending from the XhoI site at 22.9 map units, which can be ligated or recombined with plasmid DNA containing adenovirus sequences extending from 0 to 22.9 or 26.5 map units, respectively. Mutations were made by bisulfite mutagenesis in the region between base pairs -52 and -12 with respect to the cap site at +1 and transferred to the appropriate plasmids for viral reconstruction. Of 19 mutant plasmid sequences containing single or multiple G-to-A transitions, 14 could be placed in the viral genome with no apparent change in phenotype. These mutant sequences included those which contained four transitions in the string of G residues immediately downstream of the TATA box. There were no alterations in rates of transcription from the major late promoter, sites of transcription initiation, or steady-state levels of late mRNAs. All of the five mutant sequences which could not be placed in virus contained multiple transitions both up- and downstream of the TATA box. Two of these apparently lethal mutant sequences were used in promoter fusion experiments to test their ability to promote transcription of rabbit beta-globin sequences placed in the dispensable E1 region of the virus. Both sequences showed diminished ability compared with wild-type sequences to promote transcription in this context. Comparisons between these two sequences and the viable mutant sequences suggest a role for the string of G residues located between -38 and -33 in promoting transcription from the major late promoter. The data as a whole also demonstrate that the specific nucleotide sequence of this region of the major late promoter, which overlaps transcription elements of the divergent IVa2 transcription unit and coding sequences of the adenovirus DNA polymerase, is not rigidly constrained but can mutate extensively without loss of these several functions.

Adenoviridae↗
PubMed1986

Characterization of Fischer rat embryo (CREF) cells transformed by bovine papillomavirus type 1.

Transformation of an established Fischer rat embryo (CREF) cell line by bovine papillomavirus type 1 (BPV-1), in contrast to transformation by type 5 adenovirus or the T24 (Ha-ras) oncogene, resulted in transformants which did not exhibit a major increase in saturation density or a decrease in 125I-epidermal growth factor binding. BPV-1-transformed CREF clones did, however, grow in agar suspension culture and were tumorigenic in both nude mice and Fischer rats. The majority of transformed clones contained multiple extrachromosomal copies of BPV DNA. One transformed CREF clone contained integrated BPV-1 DNA which underwent sequence rearrangements following tumor formation in a Fischer rat and reestablishment in cell culture. BPV copy number varied in subclones of transformants isolated from the same monolayer focus, in agar-derived subclones of the same transformed focus, in tumors and in tumor-derived BPV-transformed CREF subclones. The degree of expression of specific transformation-related phenotypes, i.e., saturation density, growth in agar, and tumorigenicity, was not correlated with BPV copy number in transformed clones. Analysis of the biological properties of tumor-derived BPV-1-transformed CREF subclones indicated that certain transformants developed a stable increase in expression of transformation-related properties, a process termed "progression." TPA did not enhance the frequency of BPV-1 transformation or BPV DNA copy number in transformed CREF cells. The present study demonstrates that the CREF- transformation system can be utilized to study the molecular basis of BPV-1 transformation and should prove useful in studying the role of specific BPV-1 transforming proteins in regulating expression of the transformed phenotype and the mechanism by which transformed cells undergo progression of the transformed state.

Adenoviruses, Human↗
PubMed1986

Cleavage of vimentin in dense cell cultures. Inhibition upon transformation by type 5 adenovirus.

The analysis on two-dimensional isoelectric focusing and SDS polyacrylamide gels (2D gels) of the Triton X-100 and high salt-insoluble fraction of fibroblast cell lines, certain epithelial cell lines and granulosa cells revealed various amounts of a vimetin cleavage product, with a more basic pI and with a MW (1,500-2,000) lower than that of intact vimentin. This cleavage product of vimentin which constituted as much as 30% of the total vimentin in an established rat embryo fibroblast cell line (CREF), was detected by a monoclonal antivimentin antibody in whole cell and Triton-insoluble extracts, and it has a phosphorylated variant which can be degraded to form the "staircase pattern" on 2D gels similarly to intact vimentin. This processing of vimentin occurred mainly in dense cell cultures and it could not be induced in sparse cell cultures by inhibiting DNA synthesis with ara C, or by arresting cell growth in medium containing 0.1% serum. Transformation of CREF cells with intact wild-type (H5wt) and host-range cold-sensitive mutants (H5hr1 or H5d1101) of type 5 adenovirus (Ad5), or transformation of CREF cells by Ca2+-mediated DNA transfection with the transforming E1a (0-4.5 map units) or E1a + E1b (0-11.5 map units) region of Ad5 inhibits the cleavage of vimentin in dense cultures only at temperatures which are permissive for expression of the transformed phenotype. The transformation of cells with bovine papilloma virus type 1, with T24 ras oncogene, or with RSV does not interfere with the cleavage of vimentin. The organization of the vimentin network in dense cultures, where the vimentin cleavage occurs, is very different from that of sparse untransformed and sparse or dense Ad5-transformed cells. The possibility that the acidic amino acid-rich C-terminus of vimentin is cleaved in dense cell cultures in conjunction with the reorganization of the vimentin network and the inhibition of this cleavage by transformation with Ad5, are discussed.

Adenoviruses, Human↗
PubMed1986

DNase I-hypersensitive sites in the 5'-flanking region of the rat serum albumin gene: correlation between chromatin structure and transcriptional activity.

As tested by DNase I digestion, the chromatin structure in several regions 5' to the rat serum albumin gene varies in tissues and cell lines that differ in transcription rate of this gene. Three DNase I-hypersensitive regions were found in hepatocyte nuclei but not in kidney cell nuclei. The sites were approximately 2.8 kbp (site 1), 0.2 kbp (site 2), and 0.05 kbp (site 3) upstream from the cap site of the gene. In rat fetal liver tissue and rat hepatoma cell lines (FaO, C2, and C2-rev7), as well as in cultured primary hepatocytes where the rate of albumin gene transcription is lower than in adult liver, hypersensitive site (HSS) 1 was absent while sites 2 and 3 were present. In addition, the C2 cell line, which does not express albumin mRNA, contains a different HSS at position -1.5 kbp. Factors (proteins) bound to sites 2 and 3 may allow cell-specific transcription, but the additional factor interaction at site 1 could be required for a maximal rate of albumin gene transcription.

Animals↗