Regulation of the ovine MT1 melatonin receptor promoter

Interaction between multiple pituitary transcription factors at different phases of development

Jonathan D. Johnston, Carole Schuster, Perry Barrett, David G. Hazlerigg

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Pineal secretion of melatonin provides a neuroendocrine representation of the light-dark cycle, which is used to synchronise daily and annual rhythms of physiology and behaviour. In mammals, melatonin primarily acts through MT1, melatonin receptors that exhibit a highly restricted tissue distribution. Expression of MT1, receptors is subject to developmental and circadian control, which likely modulates the physiological actions of melatonin. To investigate the mechanisms controlling MT1, expression we cloned the proximal 1.5 kb region of the ovine MT1, promoter.

Sequence analysis revealed putative cis-elements for transcription factors involved in pituitary development, namely Pitx-1 and Egr-1, and multiple putative E-boxes, which are involved in both circadian and developmental gene regulation. Nuclear protein from ovine pars tuberalis (PT) cells, a site of high endogenous MT1, expression, stimulated gene expression from a MT1, expression construct, indicating the presence of a functional promoter. Pitx-1 was strongly expressed in the ovine PT and stimulated MT1, promoter activity in transfection assays. Co-transfection with Egr-1 induced promoter-specific effects: Pitx-1-stimulated MT1, activity was inhibited, whereas beta LH promoter activity was enhanced.

In addition to Pitx-1 the circadian clock genes Clock and Bmall were also expressed in the PT. However, despite multiple putative E-boxes in the MT1, promoter, transfected Clock and Bmall were unable to regulate either basal or Pitx-1-stimulated MT1, promoter activity.

The current data, in conjunction with our previous study of the rat MT1, promoter, suggests a general model in which melatonin receptor expression in the mammalian pituitary is determined by the developmentally changing balance between stimulatory and inhibitory transcription factors. Furthermore, our data suggest that circadian variation in MT1, gene expression does not depend upon the direct action of circadian clock genes on E-box cis-elements. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume268
Issue number1-2
DOIs
Publication statusPublished - 30 Mar 2007

Keywords

  • Pitx-1
  • Egr-1
  • pars distalis
  • gonadotroph
  • pars tuberalis
  • E-box
  • decoding photoperiodic time
  • hamster phodopus-sungorus
  • messenger-RNA expression
  • rat pars tuberalis
  • hormone beta-gene
  • suprachiasmatic nuclei
  • binding-sites
  • circadian clock
  • Siberian hamsters
  • Syrian-hamsters

Cite this

Regulation of the ovine MT1 melatonin receptor promoter : Interaction between multiple pituitary transcription factors at different phases of development. / Johnston, Jonathan D.; Schuster, Carole; Barrett, Perry; Hazlerigg, David G.

In: Molecular and Cellular Endocrinology, Vol. 268, No. 1-2, 30.03.2007, p. 59-66.

Research output: Contribution to journalArticle

@article{3d8c97a42f8d42acbdcbefa9a8a7e9d5,
title = "Regulation of the ovine MT1 melatonin receptor promoter: Interaction between multiple pituitary transcription factors at different phases of development",
abstract = "Pineal secretion of melatonin provides a neuroendocrine representation of the light-dark cycle, which is used to synchronise daily and annual rhythms of physiology and behaviour. In mammals, melatonin primarily acts through MT1, melatonin receptors that exhibit a highly restricted tissue distribution. Expression of MT1, receptors is subject to developmental and circadian control, which likely modulates the physiological actions of melatonin. To investigate the mechanisms controlling MT1, expression we cloned the proximal 1.5 kb region of the ovine MT1, promoter.Sequence analysis revealed putative cis-elements for transcription factors involved in pituitary development, namely Pitx-1 and Egr-1, and multiple putative E-boxes, which are involved in both circadian and developmental gene regulation. Nuclear protein from ovine pars tuberalis (PT) cells, a site of high endogenous MT1, expression, stimulated gene expression from a MT1, expression construct, indicating the presence of a functional promoter. Pitx-1 was strongly expressed in the ovine PT and stimulated MT1, promoter activity in transfection assays. Co-transfection with Egr-1 induced promoter-specific effects: Pitx-1-stimulated MT1, activity was inhibited, whereas beta LH promoter activity was enhanced.In addition to Pitx-1 the circadian clock genes Clock and Bmall were also expressed in the PT. However, despite multiple putative E-boxes in the MT1, promoter, transfected Clock and Bmall were unable to regulate either basal or Pitx-1-stimulated MT1, promoter activity.The current data, in conjunction with our previous study of the rat MT1, promoter, suggests a general model in which melatonin receptor expression in the mammalian pituitary is determined by the developmentally changing balance between stimulatory and inhibitory transcription factors. Furthermore, our data suggest that circadian variation in MT1, gene expression does not depend upon the direct action of circadian clock genes on E-box cis-elements. (c) 2007 Elsevier Ireland Ltd. All rights reserved.",
keywords = "Pitx-1, Egr-1, pars distalis, gonadotroph, pars tuberalis, E-box, decoding photoperiodic time, hamster phodopus-sungorus, messenger-RNA expression, rat pars tuberalis, hormone beta-gene, suprachiasmatic nuclei, binding-sites, circadian clock, Siberian hamsters, Syrian-hamsters",
author = "Johnston, {Jonathan D.} and Carole Schuster and Perry Barrett and Hazlerigg, {David G.}",
year = "2007",
month = "3",
day = "30",
doi = "10.1016/j.mce.2007.01.015",
language = "English",
volume = "268",
pages = "59--66",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Regulation of the ovine MT1 melatonin receptor promoter

T2 - Interaction between multiple pituitary transcription factors at different phases of development

AU - Johnston, Jonathan D.

AU - Schuster, Carole

AU - Barrett, Perry

AU - Hazlerigg, David G.

PY - 2007/3/30

Y1 - 2007/3/30

N2 - Pineal secretion of melatonin provides a neuroendocrine representation of the light-dark cycle, which is used to synchronise daily and annual rhythms of physiology and behaviour. In mammals, melatonin primarily acts through MT1, melatonin receptors that exhibit a highly restricted tissue distribution. Expression of MT1, receptors is subject to developmental and circadian control, which likely modulates the physiological actions of melatonin. To investigate the mechanisms controlling MT1, expression we cloned the proximal 1.5 kb region of the ovine MT1, promoter.Sequence analysis revealed putative cis-elements for transcription factors involved in pituitary development, namely Pitx-1 and Egr-1, and multiple putative E-boxes, which are involved in both circadian and developmental gene regulation. Nuclear protein from ovine pars tuberalis (PT) cells, a site of high endogenous MT1, expression, stimulated gene expression from a MT1, expression construct, indicating the presence of a functional promoter. Pitx-1 was strongly expressed in the ovine PT and stimulated MT1, promoter activity in transfection assays. Co-transfection with Egr-1 induced promoter-specific effects: Pitx-1-stimulated MT1, activity was inhibited, whereas beta LH promoter activity was enhanced.In addition to Pitx-1 the circadian clock genes Clock and Bmall were also expressed in the PT. However, despite multiple putative E-boxes in the MT1, promoter, transfected Clock and Bmall were unable to regulate either basal or Pitx-1-stimulated MT1, promoter activity.The current data, in conjunction with our previous study of the rat MT1, promoter, suggests a general model in which melatonin receptor expression in the mammalian pituitary is determined by the developmentally changing balance between stimulatory and inhibitory transcription factors. Furthermore, our data suggest that circadian variation in MT1, gene expression does not depend upon the direct action of circadian clock genes on E-box cis-elements. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

AB - Pineal secretion of melatonin provides a neuroendocrine representation of the light-dark cycle, which is used to synchronise daily and annual rhythms of physiology and behaviour. In mammals, melatonin primarily acts through MT1, melatonin receptors that exhibit a highly restricted tissue distribution. Expression of MT1, receptors is subject to developmental and circadian control, which likely modulates the physiological actions of melatonin. To investigate the mechanisms controlling MT1, expression we cloned the proximal 1.5 kb region of the ovine MT1, promoter.Sequence analysis revealed putative cis-elements for transcription factors involved in pituitary development, namely Pitx-1 and Egr-1, and multiple putative E-boxes, which are involved in both circadian and developmental gene regulation. Nuclear protein from ovine pars tuberalis (PT) cells, a site of high endogenous MT1, expression, stimulated gene expression from a MT1, expression construct, indicating the presence of a functional promoter. Pitx-1 was strongly expressed in the ovine PT and stimulated MT1, promoter activity in transfection assays. Co-transfection with Egr-1 induced promoter-specific effects: Pitx-1-stimulated MT1, activity was inhibited, whereas beta LH promoter activity was enhanced.In addition to Pitx-1 the circadian clock genes Clock and Bmall were also expressed in the PT. However, despite multiple putative E-boxes in the MT1, promoter, transfected Clock and Bmall were unable to regulate either basal or Pitx-1-stimulated MT1, promoter activity.The current data, in conjunction with our previous study of the rat MT1, promoter, suggests a general model in which melatonin receptor expression in the mammalian pituitary is determined by the developmentally changing balance between stimulatory and inhibitory transcription factors. Furthermore, our data suggest that circadian variation in MT1, gene expression does not depend upon the direct action of circadian clock genes on E-box cis-elements. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

KW - Pitx-1

KW - Egr-1

KW - pars distalis

KW - gonadotroph

KW - pars tuberalis

KW - E-box

KW - decoding photoperiodic time

KW - hamster phodopus-sungorus

KW - messenger-RNA expression

KW - rat pars tuberalis

KW - hormone beta-gene

KW - suprachiasmatic nuclei

KW - binding-sites

KW - circadian clock

KW - Siberian hamsters

KW - Syrian-hamsters

U2 - 10.1016/j.mce.2007.01.015

DO - 10.1016/j.mce.2007.01.015

M3 - Article

VL - 268

SP - 59

EP - 66

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

IS - 1-2

ER -