The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
5'-Heterogeneity of Glucocorticoid Receptor Messenger RNA Is Tissue Specific: Differential Regulation of Variant Transcripts by Early-Life Events
Open accessAbstract
Glucocorticoid receptor (GR) gene expression is regulated in a complex tissue-specific manner, notably by early-life environmental events that program tissue GR levels. We have identified and characterized several new rat GR mRNAs. All encode a common protein, but differ in their 5'-leader sequences as a consequence of alternate splicing of, potentially, 11 different exon 1 sequences. Most are located in a 3-kb CpG island, upstream of exon 2, that exhibits substantial promoter activity in transfected cells. Ribonuclease (RNase) protection analysis demonstrated significant levels of six alternate exons 1 in vivo in rat, with differences between liver, hippocampus, and thymus reflecting tissue-specific differences in promoter activity. Two of the alternate exons 1 (exons 1(6) and 1(10)) were expressed in all tissues examined, together present in 77-87% of total GR mRNA. The remaining GR transcripts contained tissue-specific alternate first exons. Importantly, tissue-specific first exon usage was altered by perinatal environmental manipulations. Postnatal handling, which permanently increases GR in the hippocampus, causing attenuation of stress responses, selectively elevated GR mRNA containing the hippocampus-specific exon 1(7). Prenatal glucocorticoid exposure, which increases hepatic GR expression and produces adult hyperglycemia, decreased the proportion of hepatic GR mRNA containing the predominant exon 1(10), suggesting an increase in a minor exon 1 variant. Such tissue specificity of promoter usage allows differential GR regulation and programming.
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Cited by
Epigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2270 · Cited by 3,531
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Epigenetics and the biological definition of gene×environment interactions
Meaney, M. J. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01381.x · Cited by 1,239
Self-citationMeaney, M. J., & Szyf, M. (2005) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2005.7.2/mmeaney · Cited by 958
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Metadata
- Authors
- McCormick, J. A.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-04-01
- Volume
- 14
- Issue
- 4
- Pages
- 506-517
- ISSN
- 0888-8809 (ISSN-L)
- OpenAlex
- W2145450525
- Cited by
- 265
- References
- 41
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- bronze
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