One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter

Karoline Briegel, Bernd Hentsch, Isolde Pfeuffer, Edgar Serfling

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The inducible, T cell-specific enhancers of murine and human Interleukin 2 (II-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif. When cloned in multiple copies this socalled TCEd (distal T cell element) acts as an inducible proto-enhancer element in El4 T lymphoma cells, but not in HeLa cells. In extracts of induced, II-2 secreting El4 cells three individual protein factors bind to TCEd DNA. The binding of the most prominent factor, named TCF-1 (T cell factor 1), is correlated with the protoenhancer activity of TCEd. TCF-1 consists of two polypeptides of about 50kD and 105kD; the former seems to be related to the 50kD polypeptide of NF-kB. Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA. The conversion of the TCEd to a 'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the converted' TCEd motifs in HeLa cells. Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and MeLa cells. These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the II-2 gene.

Original languageEnglish
Pages (from-to)5929-5936
Number of pages8
JournalNucleic Acids Research
Volume19
Issue number21
StatePublished - Nov 11 1991
Externally publishedYes

Fingerprint

Interleukin
T-cells
NF-kappa B
Promoter
Base Pairing
T Cell Transcription Factor 1
Interleukin-2
T-Lymphocytes
Cell
HeLa Cells
DNA
Polypeptides
Genes
Peptides
Lymphocytes
T-Cell Lymphoma
Transcription
Gene
Tight-binding
Substitution reactions

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)

Cite this

One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter. / Briegel, Karoline; Hentsch, Bernd; Pfeuffer, Isolde; Serfling, Edgar.

In: Nucleic Acids Research, Vol. 19, No. 21, 11.11.1991, p. 5929-5936.

Research output: Contribution to journalArticle

@article{d0bb0d80e2f944e99af63befdf0fb7cc,
title = "One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter",
abstract = "The inducible, T cell-specific enhancers of murine and human Interleukin 2 (II-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif. When cloned in multiple copies this socalled TCEd (distal T cell element) acts as an inducible proto-enhancer element in El4 T lymphoma cells, but not in HeLa cells. In extracts of induced, II-2 secreting El4 cells three individual protein factors bind to TCEd DNA. The binding of the most prominent factor, named TCF-1 (T cell factor 1), is correlated with the protoenhancer activity of TCEd. TCF-1 consists of two polypeptides of about 50kD and 105kD; the former seems to be related to the 50kD polypeptide of NF-kB. Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA. The conversion of the TCEd to a 'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the converted' TCEd motifs in HeLa cells. Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and MeLa cells. These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the II-2 gene.",
author = "Karoline Briegel and Bernd Hentsch and Isolde Pfeuffer and Edgar Serfling",
year = "1991",
month = "11",
day = "11",
language = "English",
volume = "19",
pages = "5929--5936",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "21",

}

TY - JOUR

T1 - One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter

AU - Briegel, Karoline

AU - Hentsch, Bernd

AU - Pfeuffer, Isolde

AU - Serfling, Edgar

PY - 1991/11/11

Y1 - 1991/11/11

N2 - The inducible, T cell-specific enhancers of murine and human Interleukin 2 (II-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif. When cloned in multiple copies this socalled TCEd (distal T cell element) acts as an inducible proto-enhancer element in El4 T lymphoma cells, but not in HeLa cells. In extracts of induced, II-2 secreting El4 cells three individual protein factors bind to TCEd DNA. The binding of the most prominent factor, named TCF-1 (T cell factor 1), is correlated with the protoenhancer activity of TCEd. TCF-1 consists of two polypeptides of about 50kD and 105kD; the former seems to be related to the 50kD polypeptide of NF-kB. Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA. The conversion of the TCEd to a 'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the converted' TCEd motifs in HeLa cells. Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and MeLa cells. These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the II-2 gene.

AB - The inducible, T cell-specific enhancers of murine and human Interleukin 2 (II-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif. When cloned in multiple copies this socalled TCEd (distal T cell element) acts as an inducible proto-enhancer element in El4 T lymphoma cells, but not in HeLa cells. In extracts of induced, II-2 secreting El4 cells three individual protein factors bind to TCEd DNA. The binding of the most prominent factor, named TCF-1 (T cell factor 1), is correlated with the protoenhancer activity of TCEd. TCF-1 consists of two polypeptides of about 50kD and 105kD; the former seems to be related to the 50kD polypeptide of NF-kB. Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA. The conversion of the TCEd to a 'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the converted' TCEd motifs in HeLa cells. Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and MeLa cells. These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the II-2 gene.

UR - http://www.scopus.com/inward/record.url?scp=0026093797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026093797&partnerID=8YFLogxK

M3 - Article

C2 - 1945879

AN - SCOPUS:0026093797

VL - 19

SP - 5929

EP - 5936

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 21

ER -