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Table of Contents
Vol. 83, No. 3-4, 2006
Issue release date: October 2006
Section title: Reviews
Neuroendocrinology 2006;83:145–153
(DOI:10.1159/000095522)

Regulation of the Human Growth Hormone Gene Family: Possible Role for Pit-1 in Early Stages of Pituitary-Specific Expression and Repression

Cattini P.A. · Yang X. · Jin Y. · Detillieux K.A.
Department of Physiology, University of Manitoba, Winnipeg, Canada

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Article / Publication Details

First-Page Preview
Abstract of Reviews

Received: May 16, 2006
Accepted: May 24, 2006
Published online: October 16, 2006
Issue release date: October 2006

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN

Abstract

The somatic cells of a multicellular organism contain an identical complement of genes that need to be expressed specifically and appropriately to allow the normal development and functions associated with an organism. In the eukaryotic cell nucleus, genes are packaged with nucleoprotein histones into chromatin. The human growth hormone (GH)/chorionic somatomammotropin (CS) gene family offers an excellent model to study the relationship between chromatin structure and transcription factor binding in terms of tissue-specific gene expression. The GH/CS gene family consists of five genes (GH-N, GH-V, CS-A, CS-B and CS-L), contained in a single locus on chromosome 17. Although they share approximately 94% sequence similarity, GH-N expression is restricted to pituitary somatotropes while the four placental GH/CS genes are expressed in the villus syncytiotrophoblast. Appropriate expression in vivo is dependent on remote sequences found 14–32 kb upstream of GH-N in the loci of adjacent genes, and these sequences are characterized by five (I–V) nuclease-hypersensitive sites (HS). Pituitary-specific factor Pit-1 binds at HS I/II and plays an essential role in chromatin remodeling and GH-N expression; however, the processes that lead to HS I/II accessibility are unknown. We discuss the possibility that Pit-1-driven remodeling at HS III may precede that at HS I/II in the pituitary. Also, in pituitary chromatin, all five GH/CS genes share similar nuclease sensitivity, suggesting that the conformation of the placental genes is not inhibitory to transcription. Given that the promoters of both GH-N and the placental GH/CS genes contain Pit-1-binding sites, possible mechanisms to restrict placenta GH/CS promoter activity in the pituitary are discussed, including active repression via P sequences located upstream of each of the placental GH/CS genes. Positively or negatively influencing those components known to be important for pituitary transcription may link epigenetic events to key transcription factors in the overall picture of tissue-specific control of gene expression.

© 2006 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Reviews

Received: May 16, 2006
Accepted: May 24, 2006
Published online: October 16, 2006
Issue release date: October 2006

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN


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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.