Identification of a novel transcriptional repressor element located in the first intron of the human BRCA1 gene.

Oncogene
T C Suen, P E Goss

Abstract

Loss or lowered expression of BRCA1 in non-familial breast cancer has been shown in several recent studies. Understanding how BRCA1 expression is regulated should provide new insights into the role of BRCA1 in sporadic breast cancer. We have recently identified a critical 18-base pair (bp) DNA element within the minimal BRCA1 promoter whereupon the formation of a specific protein-DNA complex and transcription of BRCA1 is dependent. We now report a non tissue-specific transcriptional repressor activity, located more than 500 bp into the first intron of BRCA1. Progressive deletions from the 3'-end of intron 1 and reporter gene assays localized the repressor activity to an 83-bp region. Electrophoretic mobility shift assays with this 83 bp DNA and various sub-fragments of it showed binding of nuclear proteins to a 36 bp BstNI-BseRI fragment. Functional transcriptional repression by this 36 bp DNA could be conferred on a heterologous thymidine kinase promoter. Analysis of multiple reporter gene constructs containing the BRCA1 genomic region driving transcription in both directions suggests that the putative negative regulatory element functions to block transcription only in the BRCA1 direction, although the promoter is shared by t...Continue Reading

References

Dec 1, 1990·Molecular and Cellular Biology·T C Suen, M C Hung
Jan 1, 1990·Cleveland Clinic Journal of Medicine·D H KorzickC C Simpfendorfer
Mar 25, 1989·Nucleic Acids Research·G R MacGregor, C T Caskey
Jul 1, 1989·Indian Journal of Pediatrics·M SwarnaP P Reddy
Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Apr 1, 1995·Nature Genetics·L HoskingA Jeffreys
Apr 1, 1995·Nature Genetics·S D MerajverT S Frank
Oct 7, 1994·Science·P A FutrealY Miki
Mar 1, 1996·Nature Genetics·J T HoltR A Jensen
Dec 1, 1995·Human Molecular Genetics·C F XuE Solomon
Aug 22, 1996·Nature·M S Chapman, I M Verma
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·A N MonteiroH Hanafusa
Jan 1, 1997·Current Opinion in Oncology·G Casey
May 27, 1997·Proceedings of the National Academy of Sciences of the United States of America·R ScullyJ D Parvin
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·H Ruffner, I M Verma
Aug 22, 1997·The Journal of Biological Chemistry·C F XuE Solomon
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T OuchiH Hanafusa
Apr 8, 1998·Current Opinion in Genetics & Development·D Bertwistle, A Ashworth
May 16, 1998·Biochemical and Biophysical Research Communications·G Sourvinos, D A Spandidos
May 7, 1998·The International Journal of Biochemistry & Cell Biology·A D SharrocksP R Yates
Jan 16, 1999·The Journal of Biological Chemistry·D T Haile, J D Parvin
Mar 20, 1999·The Journal of Biological Chemistry·S Thakur, C M Croce
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·R I Yarden, L C Brody
Aug 24, 1999·Nucleic Acids Research·S Philipsen, G Suske

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Citations

Mar 22, 2005·Biochimica Et Biophysica Acta·Ting-Chung SuenPaul E Goss
Nov 14, 2003·Reproductive Biology and Endocrinology : RB&E·Marcia L McCoyCalvin D Roskelley
Sep 30, 2010·International Journal of Biological Sciences·Brian J KlukSidney W Fu
Jan 10, 2013·International Journal of Clinical Oncology·Yongguo ZhangKaichun Wu
May 27, 2003·Journal of Cellular Physiology·Eliot M RosenItzhak D Goldberg
Jul 4, 2012·Human Mutation·Gaël A MillotUNKNOWN ENIGMA Consortium Functional Assay Working Group
Nov 26, 2005·International Archives of Occupational and Environmental Health·Judith BrownEwan B Macdonald
Feb 1, 2003·Breast Cancer Research : BCR·Christopher R Mueller, Calvin D Roskelley
Mar 6, 2002·The Journal of Biological Chemistry·Krzysztof Sobczak, Wlodzimierz J Krzyzosiak

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