An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro

Rajesh Bagga, Beverly Emerson

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The 3' enhancer of the T cell receptor α-chain (TCRα) gene directs the tissue- and stage-specific expression and V(D)J recombination of this gene locus. Using an in vitro system that reproduces TCRα enhancer activity efficiently, we show that long-range promoter-enhancer regulation requires a T cell-specific repressor complex and is sensitive to DNA topology. In this system, the enhancer functions to derepress the promoter on supercoiled, but not relaxed, templates. We find that the TCRα promoter is inactivated by a repressor complex that contains the architectural protein HMG I/Y. In the absence of this repressor complex, expression of the TCRα gene is completely independent of the 3' enhancer and DNA topology. The interaction of the T cell-restricted protein LEF-1 with the TCRα enhancer is required for promoter derepression. In this system, the TCRα enhancer increases the number of active promoters rather than the rate of transcription. Thus, long- range enhancers function in a distinct manner from promoters and provide the regulatory link between repressors, DNA topology, and gene activity.

Original languageEnglish (US)
Pages (from-to)629-639
Number of pages11
JournalGenes and Development
Volume11
Issue number5
DOIs
StatePublished - Mar 1 1997
Externally publishedYes

Fingerprint

Superhelical DNA
T-Cell Antigen Receptor
T-Cell Receptor Genes
HMGA1a Protein
DNA
V(D)J Recombination
T-Lymphocytes
Genes
In Vitro Techniques
Proteins

Keywords

  • derepression
  • DNA topology
  • enhancers
  • HMG I/Y
  • TCR genes
  • transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

@article{1e316966bbed4eba8aee7c7e6f8bd285,
title = "An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro",
abstract = "The 3' enhancer of the T cell receptor α-chain (TCRα) gene directs the tissue- and stage-specific expression and V(D)J recombination of this gene locus. Using an in vitro system that reproduces TCRα enhancer activity efficiently, we show that long-range promoter-enhancer regulation requires a T cell-specific repressor complex and is sensitive to DNA topology. In this system, the enhancer functions to derepress the promoter on supercoiled, but not relaxed, templates. We find that the TCRα promoter is inactivated by a repressor complex that contains the architectural protein HMG I/Y. In the absence of this repressor complex, expression of the TCRα gene is completely independent of the 3' enhancer and DNA topology. The interaction of the T cell-restricted protein LEF-1 with the TCRα enhancer is required for promoter derepression. In this system, the TCRα enhancer increases the number of active promoters rather than the rate of transcription. Thus, long- range enhancers function in a distinct manner from promoters and provide the regulatory link between repressors, DNA topology, and gene activity.",
keywords = "derepression, DNA topology, enhancers, HMG I/Y, TCR genes, transcription",
author = "Rajesh Bagga and Beverly Emerson",
year = "1997",
month = "3",
day = "1",
doi = "10.1101/gad.11.5.629",
language = "English (US)",
volume = "11",
pages = "629--639",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "5",

}

TY - JOUR

T1 - An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro

AU - Bagga, Rajesh

AU - Emerson, Beverly

PY - 1997/3/1

Y1 - 1997/3/1

N2 - The 3' enhancer of the T cell receptor α-chain (TCRα) gene directs the tissue- and stage-specific expression and V(D)J recombination of this gene locus. Using an in vitro system that reproduces TCRα enhancer activity efficiently, we show that long-range promoter-enhancer regulation requires a T cell-specific repressor complex and is sensitive to DNA topology. In this system, the enhancer functions to derepress the promoter on supercoiled, but not relaxed, templates. We find that the TCRα promoter is inactivated by a repressor complex that contains the architectural protein HMG I/Y. In the absence of this repressor complex, expression of the TCRα gene is completely independent of the 3' enhancer and DNA topology. The interaction of the T cell-restricted protein LEF-1 with the TCRα enhancer is required for promoter derepression. In this system, the TCRα enhancer increases the number of active promoters rather than the rate of transcription. Thus, long- range enhancers function in a distinct manner from promoters and provide the regulatory link between repressors, DNA topology, and gene activity.

AB - The 3' enhancer of the T cell receptor α-chain (TCRα) gene directs the tissue- and stage-specific expression and V(D)J recombination of this gene locus. Using an in vitro system that reproduces TCRα enhancer activity efficiently, we show that long-range promoter-enhancer regulation requires a T cell-specific repressor complex and is sensitive to DNA topology. In this system, the enhancer functions to derepress the promoter on supercoiled, but not relaxed, templates. We find that the TCRα promoter is inactivated by a repressor complex that contains the architectural protein HMG I/Y. In the absence of this repressor complex, expression of the TCRα gene is completely independent of the 3' enhancer and DNA topology. The interaction of the T cell-restricted protein LEF-1 with the TCRα enhancer is required for promoter derepression. In this system, the TCRα enhancer increases the number of active promoters rather than the rate of transcription. Thus, long- range enhancers function in a distinct manner from promoters and provide the regulatory link between repressors, DNA topology, and gene activity.

KW - derepression

KW - DNA topology

KW - enhancers

KW - HMG I/Y

KW - TCR genes

KW - transcription

UR - http://www.scopus.com/inward/record.url?scp=0031001394&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031001394&partnerID=8YFLogxK

U2 - 10.1101/gad.11.5.629

DO - 10.1101/gad.11.5.629

M3 - Article

C2 - 9119227

AN - SCOPUS:0031001394

VL - 11

SP - 629

EP - 639

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 5

ER -