Chromatin HMG-I (Y) as a Co-regulatory Protein for Estrogen Receptor Action in Breast Cancer Cells
Abstract
Through sequence analysis of several estrogen responsive gene promoters, we found that many of estrogen response elements (EREs) are composite elements for ER and potential adjacent or overlapping sites for the non-histone chromatin protein HMG-I(Y). Therefore, we propose that depending on the context of the target gene promoter, HMG-(Y) may either enhance or blunt the activity of ER and could contribute to cellular resistance to estrogen and antiestrogen frequently observed in breast tumors. Two estrogen responsive gene promoters, human C3 and rat prolactin which contain EREs with putative HMG-I(Y) binding sites flanking or overlapping the ERE, were used as a model. Oligonucleotides containing ERE and flanking sequences from both promoter were used in in vitro DNA binding assays. A synthetic ERE containing oligonucleotide which has no HMG-I(Y) binding sites was used as control. HMG-I(Y) was found to bind efficiently to both oligonucleotides containing ERE from C3 and prolactin promoter but did not bind to the synthetic EREs oligonucleotide. The binding of HMG-I(Y) to C3 and prolactin promoters appeared to prevent ER from binding whereas HMG-I(Y) had little effect on ER binding to the synthetic ERE oligonucleotides. These results suggest that the presence of HMG-I(Y) binding sites negatively modulates ER DNA binding
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1999
- Accession Number
- ADA368525
Entities
People
- Viroj Boonyaratanakornkit
Organizations
- University of Colorado Health