Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene

Tan-Wong, Sue Mei, French, Juliet D., Proudfoot, Nicholas J. and Brown, Melissa A. (2008) Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene. Proceedings of the National Academy of Sciences of the United States of America, 105 13: 5160-5165. doi:10.1073/pnas.0801048105


Author Tan-Wong, Sue Mei
French, Juliet D.
Proudfoot, Nicholas J.
Brown, Melissa A.
Title Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene
Formatted title
Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2008-04-01
Sub-type Article (original research)
DOI 10.1073/pnas.0801048105
Open Access Status Not Open Access
Volume 105
Issue 13
Start page 5160
End page 5165
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2009
Language eng
Subject C1
060407 Genome Structure and Regulation
060408 Genomics
920102 Cancer and Related Disorders
920507 Women's Health
Formatted abstract
The 85-kb breast cancer-associated gene BRCA1 is an established tumor suppressor gene, but its regulation is poorly understood. We demonstrate by gene conformation analysis in both human cell lines and mouse mammary tissue that gene loops are imposed on BRCA1 between the promoter, introns, and terminator region. Significantly, association between the BRCA1 promoter and terminator regions change upon estrogen stimulation and during lactational development. Loop formation is transcription-dependent, suggesting that transcriptional elongation plays an active role in BRCA1 loop formation. We show that the BRCA1 terminator region can suppress estrogen-induced transcription and so may regulate BRCA1 expression. Significantly, BRCA1 promoter and terminator interactions vary in different breast cancer cell lines, indicating that defects in BRCA1 chromatin structure may contribute to dysregulated expression of BRCA1 seen in breast tumors.
© 2008 by The National Academy of Sciences of the USA
Keyword Transcriptional regulation
Chromatin conformation
Gene repression
Mammary gland
Breast cancer
References Published under "Biological Sciences : Genetics"
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Fri, 27 Mar 2009, 13:49:27 EST by Glenda Chown on behalf of School of Chemistry & Molecular Biosciences