Negative regulation of transcription in vitro by a glucocorticoid response element is mediated by a trans-acting factor.

Langer, Shelby L.; Ostrowski, Michael C.

doi:10.1128/mcb.8.9.3872

Cited by 61 publications

(33 citation statements)

References 40 publications

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“…Previous studies of regulatory functions of the MMTV LTR pointed to sequences in the Ϫ140-to-Ϫ160 area as having negative effects, mainly on the basal level of transcription (32,39,40). A report on an activity affecting the glucocorticoid stimulation in a particular rat hepatoma cell line showed a negative effect as well (56).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Action of GA-Binding Protein and Glucocorticoid Receptor in Transcription from the Mouse Mammary Tumor Virus Promoter

Aurrekoetxea-Hernández

Buetti

2000

J Virol

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B lymphocytes are among the first cells to be infected by mouse mammary tumor virus (MMTV), and they play a crucial role in its life cycle. To study transcriptional regulation of MMTV in B cells, we have analyzed two areas of the long terminal repeat (LTR) next to the glucocorticoid receptor binding site, fp1 (at position ؊139 to ؊146 from the cap site) and fp2 (at ؊157 to ؊164). Both showed B-cell-specific protection in DNase I in vitro footprinting assays and contain binding sites for Ets transcription factors, a large family of proteins involved in cell proliferation and differentiation and oncogenic transformation. In gel retardation assays, fp1 and fp2 bound the heterodimeric Ets factor GA-binding protein (GABP) present in B-cell nuclear extracts, which was identified by various criteria: formation of dimers and tetramers, sensitivity to pro-oxidant conditions, inhibition of binding by specific antisera, and comigration of complexes with those formed by recombinant GABP. Mutations which prevented complex formation in vitro abolished glucocorticoid-stimulated transcription from an MMTV LTR linked to a reporter gene in transiently transfected B-cell lines, whereas they did not affect the basal level. Exogenously expressed GABP resulted in an increased level of hormone response of the LTR reporter plasmid and produced a synergistic effect with the coexpressed glucocorticoid receptor, indicating cooperation between the two. This is the first example of GABP cooperation with a steroid receptor, providing the opportunity for studying the integration of their intracellular signaling pathways.Mouse mammary tumor virus (MMTV) is a type B retrovirus which causes carcinomas of the mammary gland in females of susceptible mouse strains (8, 13). The carcinogenic transformation results from transcriptional activation of a particular class of cellular oncogenes (int genes; reviewed in reference 59). The mammary gland specificity of the oncogenic property of MMTV depends on the high viral replication rate and consequent high reinfection rate in the mammary epithelial cells, which are stimulated by pregnancy-related hormones. This hormonal stimulation has made the MMTV promoter the beststudied model for investigating the regulation of gene expression by steroid hormones (for a review, see references 7 and 51). Glucocorticoids, progesterone, and androgens (but not estrogens) strongly stimulate the rate of MMTV transcription through the binding of hormone-receptor complexes in the hormone regulatory element (HRE) (see Fig. 1) region of the proviral DNA, located upstream of the promoter in the long terminal repeat (LTR). Binding sites for additional transcription factors have been characterized, in particular for CTF (also called nuclear factor 1 [NF-1]) and Oct-1 in the HRE, and for mammary gland-specific factors further upstream in the LTR (reviewed in reference 31).During primary infection, MMTV is transmitted in the milk from the mother to the newborn and is taken up in the intestine, where it infects local lymphocytes (rev...

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Section: Discussionmentioning

confidence: 99%

Synergistic Action of GA-Binding Protein and Glucocorticoid Receptor in Transcription from the Mouse Mammary Tumor Virus Promoter

Aurrekoetxea-Hernández

Buetti

2000

J Virol

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“…In addition, negative regulation of the enhancer is also an important mechanism for the control of heavy-chain expression. Negative-enhancer regulation may be a general mechanism for tissue-specific expression as negativeregulatory elements also have been found that are associated with the insulin 1 gene enhancer (Laimins et al 1986;Nit et al 1986), the B-interferon gene enhancer {Goodbourn et al 1986), and viral enhancers in embryonic stem cells (Gorman et al 1985), and mouse mammary epithelial cells (Langer and Ostrowski 1988).…”

Section: Models For Enhancer Repressionmentioning

confidence: 99%

A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.

Scheuermann¹,

Chen²

1989

Genes Dev.

108

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We identified a novel nuclear protein, NF-|jiNR, that binds to multiple sites flanking the immunoglobulin heavy-chain enhancer. The expression of NF-|jiNR shows a unique developmental pattern; the activity is present in all cells representing early stages of B-cell development, but is absent from more mature cells that express a high level of immunoglobulin heavy chains. NF-|iNR also is present in most cell lines outside of the B-cell lineage (e.g., T cells, macrophages, and fibroblasts). The binding sites for NF-|jiNR correlate very well with cisacting negative regulatory elements of the heavy-chain enhancer defined previously. Indeed, when the segments bound by NF-^.NR are deleted from the enhancer, it is now found to function as a positive transcription element in T cells and macrophages. Taken together, these results suggest that NF-|jiNR may function as a negative regulator of enhancer function. The observation that the segments bound by NF-ftNR correspond to the segments bound to the nuclear matrix suggests an intriguing model not only of how enhancers might function but also of how negative regulation might occur.

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“…Nevertheless, mutations in the HRE appear to affect differentially the response to these diverse steroid hormones (Gowland & Buetti, 1989) (Langer & Ostrowski, 1988) (Fig. 1).…”

Section: Steroid Hormonesmentioning

confidence: 99%

Factors controlling the expression of mouse mammary tumour virus

Günzburg

Salmons

1992

Biochemical Journal

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Negative regulation of transcription in vitro by a glucocorticoid response element is mediated by a trans-acting factor.

Cited by 61 publications

References 40 publications

Synergistic Action of GA-Binding Protein and Glucocorticoid Receptor in Transcription from the Mouse Mammary Tumor Virus Promoter

Synergistic Action of GA-Binding Protein and Glucocorticoid Receptor in Transcription from the Mouse Mammary Tumor Virus Promoter

A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.

Factors controlling the expression of mouse mammary tumour virus

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