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PMID: 15498926 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors.

Nucleic acids research ·Vol. 32 ·No. 18 ·2004-00-00 ·Pages 5693-702

Hollenhorst PC, Jones DA, Graves BJ

Abstract

Sequence-specific DNA binding proteins that function as transcription factors are frequently encoded by gene families. Such proteins display highly conserved DNA binding properties, yet are expected to retain promoter selectivity. In this report we investigate this problem using the ets gene family, a group of metazoan genes whose members regulate cell growth and differentiation and are mutated in human cancers. We tested whether the level of mRNA can serve as a specificity determinant. The mRNA levels of the 27 paralogous human ets genes were measured in 23 tissues and cell lines. Real-time RT-PCR provided accurate measurement of absolute mRNA levels for each gene down to one copy per cell. Surprisingly, at least 16 paralogs were expressed in each cell sample and over half were expressed ubiquitously. Tissues and complementary cell lines showed similar expression patterns, indicating that tissue complexity was not a limitation. There was no unique, highly expressed gene for each cell type. Instead, one of only eight ets genes showed the highest expression in all samples. DNA binding studies illustrate both overlapping and unique specificities for ubiquitous ETS proteins. These findings establish the parameters of the promoter specificity dilemma within the ets family of transcription factors.

MeSH Terms
Binding Sites Cell Line DNA/metabolism DNA-Binding Proteins/biosynthesis,genetics,metabolism Gene Expression Profiling Humans Promoter Regions, Genetic Proto-Oncogene Proteins/biosynthesis,genetics,metabolism Proto-Oncogene Proteins c-ets RNA, Messenger/metabolism Reverse Transcriptase Polymerase Chain Reaction Transcription Factors/biosynthesis,genetics,metabolism
Chemicals
DNA-Binding Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-ets RNA, Messenger Transcription Factors DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hollenhorst Peter C
Department of Oncological Sciences, Huntsman Cancer Institute, 2000 Circle of Hope, University of Utah, Salt Lake City, UT 84112, USA.
Jones David A
Graves Barbara J
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkh906
Published
2004-00-00
Epub
2004-00-21
Pages
5693-702
Language
English
Region
England
NLM ID
0411011
PMCID
PMC524310
Subset
IM
Grants
NIGMS NIH HHS · GM38663 · United States
NCI NIH HHS · T32 CA93247 · United States
NCI NIH HHS · T32 CA093247 · United States
NIGMS NIH HHS · R01 GM038663 · United States
NCI NIH HHS · CA24014 · United States
NCI NIH HHS · P30 CA042014 · United States
External Links
PubMed source DOI: 10.1093/nar/gkh906 PMC Full Text View journal details
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