Publication Date:
1990-11-09
Description:
Expression of the human T cell receptor (TCR) alpha gene is regulated by a T cell-specific transcriptional enhancer that is located 4.5 kilobases (kb) 3' to the C alpha gene segment. The core enhancer contains two nuclear protein binding sites, T alpha 1 and T alpha 2, which are essential for full enhancer activity. T alpha 1 contains a consensus cyclic adenosine monophosphate (cAMP) response element (CRE) and binds a set of ubiquitously expressed CRE binding proteins. In contrast, the transcription factors that interact with the T alpha 2 site have not been defined. In this report, a lambda gt11 expression protocol was used to isolate a complementary DNA (cDNA) that programs the expression of a T alpha 2 binding protein. DNA sequence analysis demonstrated that this clone encodes the human ets-1 proto-oncogene. Lysogen extracts produced with this cDNA clone contained a beta-galactosidase-Ets-1 fusion protein that bound specifically to a synthetic T alpha 2 oligonucleotide. The Ets-1 binding site was localized to a 17-base pair (bp) region from the 3' end of T alpha 2. Mutation of five nucleotides within this sequence abolished both Ets-1 binding and the activity of the TCR alpha enhancer in T cells. These results demonstrate that Ets-1 binds in a sequence-specific fashion to the human TCR alpha enhancer and suggest that this developmentally regulated proto-oncogene functions in regulating TCR alpha gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ho, I C -- Bhat, N K -- Gottschalk, L R -- Lindsten, T -- Thompson, C B -- Papas, T S -- Leiden, J M -- AI-29673/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 9;250(4982):814-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Ann Arbor, MI.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237431" target="_blank"〉PubMed〈/a〉
Keywords:
Base Sequence
;
Binding, Competitive
;
Cloning, Molecular
;
DNA/genetics
;
DNA Mutational Analysis
;
*Enhancer Elements, Genetic
;
Gene Expression Regulation
;
Gene Rearrangement, T-Lymphocyte
;
Humans
;
Immunoblotting
;
Molecular Sequence Data
;
Proto-Oncogene Protein c-ets-1
;
Proto-Oncogene Proteins/genetics/*metabolism
;
Proto-Oncogene Proteins c-ets
;
*Proto-Oncogenes
;
Receptors, Antigen, T-Cell/genetics/*metabolism
;
Transcription Factors
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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