Cell-specific glucocorticoid repression of calcitonin/calcitonin gene-related peptide transcription. Localization to an 18-base pair basal enhancer element

Lois A Tverberg; Andrew F Russo

doi:10.1016/S0021-9258(19)37080-2

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Cell-specific glucocorticoid repression of calcitonin/calcitonin gene-related peptide transcription. Localization to an 18-base pair basal enhancer element

Journal article

Open access

Peer reviewed

Cell-specific glucocorticoid repression of calcitonin/calcitonin gene-related peptide transcription. Localization to an 18-base pair basal enhancer element

Lois A Tverberg and Andrew F Russo

The Journal of biological chemistry, Vol.267(25), pp.17567-17573

09/05/1992

DOI: 10.1016/S0021-9258(19)37080-2

PMID: 1517207

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Abstract

We have investigated the mechanisms underlying cell-specific glucocorticoid repression of calcitonin/calcitonin gene-related peptide (CGRP) gene expression. Treatment with the synthetic glucocorticoid dexamethasone has been shown to decrease mRNA levels in the 44-2C thyroid C cell line. Nuclear run-on assays showed that dexamethasone repressed transcription 2-3-fold in 44-2C cells. In contrast, dexamethasone stimulated calcitonin/CGRP transcription 4-6-fold in the CA77 thyroid C cell line. Transient transfection assays were used to map repression of reporter gene activity in 44-2C cells to a neuroendocrine cell-specific enhancer located between -920 and -1125 base pairs (bp). Within this region, an 18-bp element was found that conferred both full basal enhancer activity and dexamethasone-dependent repression in 44-2C cells. The 18-bp region contains possible binding sites for AP-1 and helix-loop-helix transcription factors as well as a glucocorticoid receptor half-site. Colocalization of repression and enhancer activity was then investigated in other cell lines. In CA77 cells, while the 920-1125 region strongly enhanced transcription, the 18-bp region conferred only partial activation and dexamethasone had little effect on reporter gene activity. Dexamethasone did not repress the calcitonin/CGRP activity in the heterologous HeLa and Rat1 fibroblast cell lines. These results suggest that glucocorticoids repress transcription of the calcitonin/CGRP gene by inhibiting cell-specific transcription factor activity.

Cell Line

Transcription, Genetic - drug effects

Calcitonin - biosynthesis

Humans

RNA, Messenger - genetics

Molecular Sequence Data

Calcitonin Gene-Related Peptide - genetics

Calcitonin - genetics

RNA, Messenger - metabolism

Gene Expression Regulation - drug effects

Transcription Factors - metabolism

Animals

Cell Nucleus - metabolism

Dexamethasone - pharmacology

Enhancer Elements, Genetic

Base Composition

Base Sequence

Calcitonin Gene-Related Peptide - biosynthesis

HeLa Cells

Cell Nucleus - drug effects

Binding Sites

Details

Title: Subtitle: Cell-specific glucocorticoid repression of calcitonin/calcitonin gene-related peptide transcription. Localization to an 18-base pair basal enhancer element
Creators: Lois A Tverberg - Department of Physiology and Biophysics, University of Iowa, Iowa City 52242
Andrew F Russo
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.267(25), pp.17567-17573
DOI: 10.1016/S0021-9258(19)37080-2
PMID: 1517207
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: R01 HD25969 / NICHD NIH HHS DK25295 / NIDDK NIH HHS
Language: English
Date published: 09/05/1992
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
Record Identifier: 9984020848902771

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