Structural and Functional Organization of the Gene Encoding the Human Thyrotropin‐Releasing Hormone Receptor

Structural and Functional Organization of the Gene Encoding the Human Thyrotropin‐Releasing... Abstract : The thyrotropin‐releasing hormone (TRH) receptor (TRHR) is widely distributed throughout the central and peripheral nervous systems. In addition to its role in controlling the synthesis and secretion of thyroid‐stimulating hormone and prolactin from the anterior pituitary, TRH is believed to act as a neurotransmitter as well as a neuromodulator. We have isolated genomic λ and P1‐derived artificial chromosome clones encoding the human TRHR. The gene was found to be 35 kb with three exons and two introns. A 541‐bp intron 1 (‐629 to ‐89 relative to the translation start site) is conserved between human and mouse. A large intron 2 of 31 kb disrupts the open reading frame (starting in position +790) in the sequence encoding the supposed junction between the third intracellular loop and the putative sixth transmembrane domain. A similar intron was found in chimpanzee and sheep but not in rat and mouse. Promoter analysis of upstream regions demonstrated cell type‐specific reporter activation, and sequencing of 2.5 kb of the promoter revealed putative cis‐acting regulatory elements for several transcription factors that may contribute to the regulation of the TRHR gene expression. Functional analysis of potential response elements for the anterior pituitary‐specific transcription factor Pit‐1 revealed cell type‐specific binding that was competed out with a Pit‐1 response element from the GH gene promoter. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Structural and Functional Organization of the Gene Encoding the Human Thyrotropin‐Releasing Hormone Receptor

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© International Society for Neurochemistry
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1046/j.1471-4159.1999.0720040.x
Publisher site
See Article on Publisher Site

Abstract

Abstract : The thyrotropin‐releasing hormone (TRH) receptor (TRHR) is widely distributed throughout the central and peripheral nervous systems. In addition to its role in controlling the synthesis and secretion of thyroid‐stimulating hormone and prolactin from the anterior pituitary, TRH is believed to act as a neurotransmitter as well as a neuromodulator. We have isolated genomic λ and P1‐derived artificial chromosome clones encoding the human TRHR. The gene was found to be 35 kb with three exons and two introns. A 541‐bp intron 1 (‐629 to ‐89 relative to the translation start site) is conserved between human and mouse. A large intron 2 of 31 kb disrupts the open reading frame (starting in position +790) in the sequence encoding the supposed junction between the third intracellular loop and the putative sixth transmembrane domain. A similar intron was found in chimpanzee and sheep but not in rat and mouse. Promoter analysis of upstream regions demonstrated cell type‐specific reporter activation, and sequencing of 2.5 kb of the promoter revealed putative cis‐acting regulatory elements for several transcription factors that may contribute to the regulation of the TRHR gene expression. Functional analysis of potential response elements for the anterior pituitary‐specific transcription factor Pit‐1 revealed cell type‐specific binding that was competed out with a Pit‐1 response element from the GH gene promoter.

Journal

Journal of NeurochemistryWiley

Published: Jan 1, 1999

Keywords: ; ; ; ; ;

References

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