Egr1 involvement in evening gene regulation by melatonin

J. M. Fustin, H. Dardente, G. C. Wagner, D. A. Carter, J. D. Johnston, G. A. Lincoln, D. G. Hazlerigg

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Seasonal photoperiodic responses in mammals depend on the pineal hormone melatonin. The pars tuberalis (PT) region of the anterior pituitary has emerged as a principal melatonin target tissue, controlling endocrine responses. Rising melatonin levels acutely influence the expression of a small cluster of genes either positively (exemplified by cryptochrome-1, cry1) or negatively (exemplified by the type 1 melatonin receptor, mt1). The purpose of this study was to characterize the pathways through which these evening actions of melatonin are mediated. In vitro experiments showed that cAMP signaling in the PT directly influences mt1 but not cry1 expression. Analysis of nuclear extracts from sheep PT tissue collected 90 min after melatonin or saline control injections highlighted the response element for the immediate early gene egr1 (EGR1-RE) as a candidate for acute melatonin-dependent transcriptional regulation. We identified putative EGR1-RE's in the proximal promoter regions of the ovine cry1 and mt1 genes, and confirmed their functionality in luciferase reporter assays. Egr1 expression is suppressed by melatonin in PT cell cultures, and is rhythmic in the ovine PT with a nadir in the early night. We propose that melatonin-dependent effects on EGR1-RE's contribute to evening gene expression profiles in this pituitary melatonin target tissue.-Fustin J. M., Dardente H., Wagner G. C., Carter D. A., Johnston J. D., Lincoln G. A., Hazlerigg D. G. Egr1 involvement in evening gene regulation by melatonin. FASEB J. 23, 764-773 (2009)

Original languageEnglish
Pages (from-to)764-773
Number of pages10
JournalThe FASEB Journal
Volume23
Issue number3
Early online date19 Nov 2008
DOIs
Publication statusPublished - Mar 2009

Keywords

  • pars tuberalis
  • clock gene
  • cryptochrome
  • photoperiod
  • circadian
  • hormone-beta-gene
  • decoding photoperiodic time
  • early growth response-1
  • steroidogenic factor-I
  • ovine pars tuberalis
  • pituitary homeobox 1
  • NGFI-A
  • suprachiasmatic nucleus
  • transcription factors
  • binding-sites

Cite this

Fustin, J. M., Dardente, H., Wagner, G. C., Carter, D. A., Johnston, J. D., Lincoln, G. A., & Hazlerigg, D. G. (2009). Egr1 involvement in evening gene regulation by melatonin. The FASEB Journal, 23(3), 764-773. https://doi.org/10.1096/fj.08-121467

Egr1 involvement in evening gene regulation by melatonin. / Fustin, J. M.; Dardente, H.; Wagner, G. C.; Carter, D. A.; Johnston, J. D.; Lincoln, G. A.; Hazlerigg, D. G.

In: The FASEB Journal, Vol. 23, No. 3, 03.2009, p. 764-773.

Research output: Contribution to journalArticle

Fustin, JM, Dardente, H, Wagner, GC, Carter, DA, Johnston, JD, Lincoln, GA & Hazlerigg, DG 2009, 'Egr1 involvement in evening gene regulation by melatonin', The FASEB Journal, vol. 23, no. 3, pp. 764-773. https://doi.org/10.1096/fj.08-121467
Fustin JM, Dardente H, Wagner GC, Carter DA, Johnston JD, Lincoln GA et al. Egr1 involvement in evening gene regulation by melatonin. The FASEB Journal. 2009 Mar;23(3):764-773. https://doi.org/10.1096/fj.08-121467
Fustin, J. M. ; Dardente, H. ; Wagner, G. C. ; Carter, D. A. ; Johnston, J. D. ; Lincoln, G. A. ; Hazlerigg, D. G. / Egr1 involvement in evening gene regulation by melatonin. In: The FASEB Journal. 2009 ; Vol. 23, No. 3. pp. 764-773.
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AU - Dardente, H.

AU - Wagner, G. C.

AU - Carter, D. A.

AU - Johnston, J. D.

AU - Lincoln, G. A.

AU - Hazlerigg, D. G.

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N2 - Seasonal photoperiodic responses in mammals depend on the pineal hormone melatonin. The pars tuberalis (PT) region of the anterior pituitary has emerged as a principal melatonin target tissue, controlling endocrine responses. Rising melatonin levels acutely influence the expression of a small cluster of genes either positively (exemplified by cryptochrome-1, cry1) or negatively (exemplified by the type 1 melatonin receptor, mt1). The purpose of this study was to characterize the pathways through which these evening actions of melatonin are mediated. In vitro experiments showed that cAMP signaling in the PT directly influences mt1 but not cry1 expression. Analysis of nuclear extracts from sheep PT tissue collected 90 min after melatonin or saline control injections highlighted the response element for the immediate early gene egr1 (EGR1-RE) as a candidate for acute melatonin-dependent transcriptional regulation. We identified putative EGR1-RE's in the proximal promoter regions of the ovine cry1 and mt1 genes, and confirmed their functionality in luciferase reporter assays. Egr1 expression is suppressed by melatonin in PT cell cultures, and is rhythmic in the ovine PT with a nadir in the early night. We propose that melatonin-dependent effects on EGR1-RE's contribute to evening gene expression profiles in this pituitary melatonin target tissue.-Fustin J. M., Dardente H., Wagner G. C., Carter D. A., Johnston J. D., Lincoln G. A., Hazlerigg D. G. Egr1 involvement in evening gene regulation by melatonin. FASEB J. 23, 764-773 (2009)

AB - Seasonal photoperiodic responses in mammals depend on the pineal hormone melatonin. The pars tuberalis (PT) region of the anterior pituitary has emerged as a principal melatonin target tissue, controlling endocrine responses. Rising melatonin levels acutely influence the expression of a small cluster of genes either positively (exemplified by cryptochrome-1, cry1) or negatively (exemplified by the type 1 melatonin receptor, mt1). The purpose of this study was to characterize the pathways through which these evening actions of melatonin are mediated. In vitro experiments showed that cAMP signaling in the PT directly influences mt1 but not cry1 expression. Analysis of nuclear extracts from sheep PT tissue collected 90 min after melatonin or saline control injections highlighted the response element for the immediate early gene egr1 (EGR1-RE) as a candidate for acute melatonin-dependent transcriptional regulation. We identified putative EGR1-RE's in the proximal promoter regions of the ovine cry1 and mt1 genes, and confirmed their functionality in luciferase reporter assays. Egr1 expression is suppressed by melatonin in PT cell cultures, and is rhythmic in the ovine PT with a nadir in the early night. We propose that melatonin-dependent effects on EGR1-RE's contribute to evening gene expression profiles in this pituitary melatonin target tissue.-Fustin J. M., Dardente H., Wagner G. C., Carter D. A., Johnston J. D., Lincoln G. A., Hazlerigg D. G. Egr1 involvement in evening gene regulation by melatonin. FASEB J. 23, 764-773 (2009)

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KW - decoding photoperiodic time

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KW - steroidogenic factor-I

KW - ovine pars tuberalis

KW - pituitary homeobox 1

KW - NGFI-A

KW - suprachiasmatic nucleus

KW - transcription factors

KW - binding-sites

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