T cell-specific protein-DNA interactions occurring at the CD4 locus

Identification of possible transcriptional control elements of the murine CD4 gene

John F. Sands, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The c/s-acting transcriptional control elements of the murine CD4 gene were investigated within 75 kb of chromatin associated with the CD4 locus. DNase I hypersensitive (DH) sites were identified in several T and non-T cell lines, and in freshly isolated thymocytes. A total of 22 DH sites were found, seven of which are present only in T cells expressing CD4 or CD8. The T cell-specific DH sites are located in four regions: (i) 5' of the first exon of CD4, (ii) in the first intron, (iii) near the second and third exons, and (iv) 3' of the CD4 gene. Some of these sites inversely correlate to the CD4 expression at defined stages of T cell development, suggesting a role for these sites in repression of this gene. The T cell-specific DH sites were subcloned and analyzed for protein-DNA interactions using the electrophoretic mobility shift assay. All T cell-specific DH sites analyzed appear to be a consequence of T cell-specific protein - DNA interactions. We have also identified the nuclear matrix attachment regions (MARs) and repetitive elements associated with the CD4 gene. Two nuclear MARs, separated by a region of highly repetitive DNA, are located 5' of the gene. Another region of highly repetitive DNA exists within the third intron. We discuss the implications of our results for the developmental regulation of CD4 expression.

Original languageEnglish (US)
Pages (from-to)1183-1194
Number of pages12
JournalInternational Immunology
Volume4
Issue number10
DOIs
StatePublished - Oct 1992
Externally publishedYes

Fingerprint

T-cells
Deoxyribonuclease I
Locus
DNA
Genes
Gene
Proteins
Protein
T-Lymphocytes
Matrix Attachment Regions
Interaction
Nuclear Matrix
Nucleic Acid Repetitive Sequences
T Cell Development
Introns
Exons
Chromatin
Electrophoretic mobility
Correlate
Electrophoretic Mobility Shift Assay

Keywords

  • CD4
  • DNase I hypersensitive sites
  • T cell development
  • Transcriptional control

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Transplantation
  • Immunology

Cite this

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abstract = "The c/s-acting transcriptional control elements of the murine CD4 gene were investigated within 75 kb of chromatin associated with the CD4 locus. DNase I hypersensitive (DH) sites were identified in several T and non-T cell lines, and in freshly isolated thymocytes. A total of 22 DH sites were found, seven of which are present only in T cells expressing CD4 or CD8. The T cell-specific DH sites are located in four regions: (i) 5' of the first exon of CD4, (ii) in the first intron, (iii) near the second and third exons, and (iv) 3' of the CD4 gene. Some of these sites inversely correlate to the CD4 expression at defined stages of T cell development, suggesting a role for these sites in repression of this gene. The T cell-specific DH sites were subcloned and analyzed for protein-DNA interactions using the electrophoretic mobility shift assay. All T cell-specific DH sites analyzed appear to be a consequence of T cell-specific protein - DNA interactions. We have also identified the nuclear matrix attachment regions (MARs) and repetitive elements associated with the CD4 gene. Two nuclear MARs, separated by a region of highly repetitive DNA, are located 5' of the gene. Another region of highly repetitive DNA exists within the third intron. We discuss the implications of our results for the developmental regulation of CD4 expression.",
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T2 - Identification of possible transcriptional control elements of the murine CD4 gene

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N2 - The c/s-acting transcriptional control elements of the murine CD4 gene were investigated within 75 kb of chromatin associated with the CD4 locus. DNase I hypersensitive (DH) sites were identified in several T and non-T cell lines, and in freshly isolated thymocytes. A total of 22 DH sites were found, seven of which are present only in T cells expressing CD4 or CD8. The T cell-specific DH sites are located in four regions: (i) 5' of the first exon of CD4, (ii) in the first intron, (iii) near the second and third exons, and (iv) 3' of the CD4 gene. Some of these sites inversely correlate to the CD4 expression at defined stages of T cell development, suggesting a role for these sites in repression of this gene. The T cell-specific DH sites were subcloned and analyzed for protein-DNA interactions using the electrophoretic mobility shift assay. All T cell-specific DH sites analyzed appear to be a consequence of T cell-specific protein - DNA interactions. We have also identified the nuclear matrix attachment regions (MARs) and repetitive elements associated with the CD4 gene. Two nuclear MARs, separated by a region of highly repetitive DNA, are located 5' of the gene. Another region of highly repetitive DNA exists within the third intron. We discuss the implications of our results for the developmental regulation of CD4 expression.

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