Transcriptional and post-transcriptional control of specific messenger RNAs in adult and embryonic liver

Powell, D. J.; Friedman, Jan M.; Oulette, A.J.; Krauter, Kenneth; Darnell, James

doi:10.1016/0022-2836(84)90304-8

Cited by 111 publications

(86 citation statements)

References 25 publications

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“…As expected, the data reveal that RNA polymerase II transcribes the albumin (Tilghman and Belayew 1982;Powell et al 1984) and tyrosine aminotransferase (Scherer et al 1982) genes at a high rate in liver. We de tect slight transcription of albumin in the kidney in this and other hybridizations (data not shown) and no signifi cant albumin transcription in the spleen.…”

Section: Differential Transcription Of the Albumin Genementioning

confidence: 52%

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.

Liu¹,

Bergman²,

Zaret³

1988

Genes Dev.

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In this paper we characterize the chromatin structure and nuclear proteins associated with different transcriptional states of the mouse serum albumin gene. We found the albumin gene to be transcribed in liver at rates 1000-fold or greater than in other tissues tested. We discovered seven DNase I hypersensitive sites encompassing the albumin gene only in liver chromatin, with strong hypersensitivity at the promoter and the enhancer, which is over 10 kb upstream. Using a gel retardation assay, we found a liver nuclear protein, or set of proteins, which binds specifically to DNA of a liver-specific hypersensitive site that maps 3.5 kb upstream, between the promoter and enhancer. Footprinting, heat insensitivity, and binding competition experiments indicate that the protein(s) have characteristics similar to a heat-stable, liver-abundant protein that binds to the albumin promoter and other enhancer and promoter sequences. Finally, we asked whether the liver-specific factors that cause DNase I hypersensitivity in vivo are present concurrently at the various sites in chromatin. We devised a simple new method to reveal that in liver, individual albumin genes are hypersensitive simultaneously at the promoter, the enhancer, and the -3.5-kb site. Thus, transcriptionally active albumin genes appear to contain tissue-abundant factors that are present at three widely spaced points in chromatin, yet at the same point in time. Similar factors binding simultaneously to at least two of these sites could create a specific structure in chromatin required for high-level albumin gene transcription.

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Section: Differential Transcription Of the Albumin Genementioning

confidence: 52%

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.

Liu¹,

Bergman²,

Zaret³

1988

Genes Dev.

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“…However, whether the expression of a given gene is controlled in different tissues by distinct regulatory elements and distinct trans-acting regulatory factors is not yet known. Likewise, even though the MUP II, IV, and V mRNAs are processed in the same manner in all tissues, the same species of MUP mRNAs may, in different tissues, exhibit different stability (6,12).…”

Section: Resultsmentioning

confidence: 99%

Expression of six mouse major urinary protein genes in the mammary, parotid, sublingual, submaxillary, and lachrymal glands and in the liver.

Shahan¹,

Denaro²,

Gilmartin³

et al. 1987

Mol. Cell. Biol.

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Mouse major urinary proteins (MUPs) are encoded by a family of about 35 to 40 highly conserved genes. In the preceding paper (K. Shahan, M. Gilmartin, and E. Derman, Mol. Cell. Biol. 7:1938-1946, 1987, we presented the sequences of the most abundant MUP mRNAs in the liver (MUP I, II, and III) and in the lachrymal (MUP IV) and submaxillary (MUP V) glands. We have shown that these five mRNAs are coded by five distinct genes, MUP I through V. In the present communication, we examine the expression of MUP genes in all of the six tissues in which MUP mRNAs are synthesized, the mammary, parotid, sublingual, lachrymal, and submaxillary glands and the liver. We show that gene MUP II is expressed in the liver and in the mammary gland, that gene MUP IV is expressed in the lachrymal and parotid glands, and that gene MUP V is expressed in the submaxillary, sublingual, and lachrymal glands. Furthermore, we present evidence that in addition to genes MUP I through V, another gene, MUP VI, is expressed in BALB/c mice in the parotid gland. The tissue-specific synthesis of MUP mRNAs is thus brought about by two major mechanisms: the expression, in different tissues, of different members of the family and the expression of a single gene at various levels in different tissues. When a particular MUP gene is expressed in several tissues, transcripts of this gene initiate at the same site and are spliced and polyadenylated in the same manner.The mouse major urinary proteins (MUPs) are secretory proteins encoded by a family of genes that exhibit sequence conservation of at least 85%, both in the transcribed and in the flanking sequences (4; Y. Shi and E. Derman, unpublished data). MUPs are synthesized in six different tissues: the liver and the lachrymal, submaxillary, parotid, sublingual, and mammary glands (14, 16). In the liver, MUPs are synthesized in response to several hormones such as testosterone, growth hormone, glucocorticoid hormones, and thyroxine and only in post-pubescent mice (10, 16). In contrast, in the submaxillary and lachrymal glands, MUPs are synthesized in prepubescent mice as well as in adult mice (16). The hormonal regulation in these two glands, however, does vary. Whereas the synthesis of MUPs in the submaxillary gland does not appear to be hormonally controlled, the synthesis of the lachrymal gland MUPs is regulated by testosterone (16).In the preceding paper (15), we described the sequences of the major species of MUP mRNAs in the liver and in the lachrymal and submaxillary glands, MUP I, II, III, IV, and V. These five mRNAs are encoded by five distinct members of the MUP gene family. The focus of the studies presented here is to examine the synthesis of MUP mRNAs in three additional tissues, the mammary, parotid, and sublingual glands, and to define the expression of each of the previously identified genes, MUPI to V. To this end, we characterized the expression of individual MUP genes with the synthetic oligonucleotide probes described in the preceding paper (15), in male and in female mice and at various ...

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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%

α3β1-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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Transcriptional and post-transcriptional control of specific messenger RNAs in adult and embryonic liver

Cited by 111 publications

References 25 publications

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.

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.

Expression of six mouse major urinary protein genes in the mammary, parotid, sublingual, submaxillary, and lachrymal glands and in the liver.

α3β1-integrin as a critical mediator of the hepatic differentiation response to the extracellular matrix

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