Transforming growth factor β1 repression of the HLA-DRα gene is mediated by conserved proximal promoter elements

A. M. Reimold, C. J. Kara, J. W. Rooney, L. H. Glimcher

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that decreases the expression of class II MHC Ag in the melanoma cell line Hs294T(c). To investigate the mechanism of this repression, we have examined the effect of TGF-β1 on expression of the HLA-DRα gene. Both the constitutive level of HLA-DR protein and DRα mRNA were repressed by treatment with TGF-β1. The proximal 176 bp of the DRα promoter were sufficient to confer TGF-β1 repression on a reporter gene. Deletional and mutational analysis of the DRα promoter revealed that the conserved S and X1 promoter elements were important for basal expression of DRα and also mediated the down-regulation by TGF-β1. Mobility shift assays and in vivo footprinting showed no change in occupancy of the proximal DRα promoter after TGF-β1 treatment. These results identify the DNA elements that mediate repression of the HLA-DRα gene by TGF-β1 and suggest that TGF- β1 acts at these sites without causing a change in promoter occupancy.

Original languageEnglish (US)
Pages (from-to)4173-4182
Number of pages10
JournalJournal of Immunology
Volume151
Issue number8
StatePublished - 1993

Fingerprint

Transforming Growth Factors
HLA-DR Antigens
Genes
Electrophoretic Mobility Shift Assay
Reporter Genes
Melanoma
Down-Regulation
Cytokines
Cell Line
Messenger RNA
DNA
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Transforming growth factor β1 repression of the HLA-DRα gene is mediated by conserved proximal promoter elements. / Reimold, A. M.; Kara, C. J.; Rooney, J. W.; Glimcher, L. H.

In: Journal of Immunology, Vol. 151, No. 8, 1993, p. 4173-4182.

Research output: Contribution to journalArticle

@article{59ab1a0f6de64363b4ad0f41a4b3dc1b,
title = "Transforming growth factor β1 repression of the HLA-DRα gene is mediated by conserved proximal promoter elements",
abstract = "Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that decreases the expression of class II MHC Ag in the melanoma cell line Hs294T(c). To investigate the mechanism of this repression, we have examined the effect of TGF-β1 on expression of the HLA-DRα gene. Both the constitutive level of HLA-DR protein and DRα mRNA were repressed by treatment with TGF-β1. The proximal 176 bp of the DRα promoter were sufficient to confer TGF-β1 repression on a reporter gene. Deletional and mutational analysis of the DRα promoter revealed that the conserved S and X1 promoter elements were important for basal expression of DRα and also mediated the down-regulation by TGF-β1. Mobility shift assays and in vivo footprinting showed no change in occupancy of the proximal DRα promoter after TGF-β1 treatment. These results identify the DNA elements that mediate repression of the HLA-DRα gene by TGF-β1 and suggest that TGF- β1 acts at these sites without causing a change in promoter occupancy.",
author = "Reimold, {A. M.} and Kara, {C. J.} and Rooney, {J. W.} and Glimcher, {L. H.}",
year = "1993",
language = "English (US)",
volume = "151",
pages = "4173--4182",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Transforming growth factor β1 repression of the HLA-DRα gene is mediated by conserved proximal promoter elements

AU - Reimold, A. M.

AU - Kara, C. J.

AU - Rooney, J. W.

AU - Glimcher, L. H.

PY - 1993

Y1 - 1993

N2 - Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that decreases the expression of class II MHC Ag in the melanoma cell line Hs294T(c). To investigate the mechanism of this repression, we have examined the effect of TGF-β1 on expression of the HLA-DRα gene. Both the constitutive level of HLA-DR protein and DRα mRNA were repressed by treatment with TGF-β1. The proximal 176 bp of the DRα promoter were sufficient to confer TGF-β1 repression on a reporter gene. Deletional and mutational analysis of the DRα promoter revealed that the conserved S and X1 promoter elements were important for basal expression of DRα and also mediated the down-regulation by TGF-β1. Mobility shift assays and in vivo footprinting showed no change in occupancy of the proximal DRα promoter after TGF-β1 treatment. These results identify the DNA elements that mediate repression of the HLA-DRα gene by TGF-β1 and suggest that TGF- β1 acts at these sites without causing a change in promoter occupancy.

AB - Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that decreases the expression of class II MHC Ag in the melanoma cell line Hs294T(c). To investigate the mechanism of this repression, we have examined the effect of TGF-β1 on expression of the HLA-DRα gene. Both the constitutive level of HLA-DR protein and DRα mRNA were repressed by treatment with TGF-β1. The proximal 176 bp of the DRα promoter were sufficient to confer TGF-β1 repression on a reporter gene. Deletional and mutational analysis of the DRα promoter revealed that the conserved S and X1 promoter elements were important for basal expression of DRα and also mediated the down-regulation by TGF-β1. Mobility shift assays and in vivo footprinting showed no change in occupancy of the proximal DRα promoter after TGF-β1 treatment. These results identify the DNA elements that mediate repression of the HLA-DRα gene by TGF-β1 and suggest that TGF- β1 acts at these sites without causing a change in promoter occupancy.

UR - http://www.scopus.com/inward/record.url?scp=0027378549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027378549&partnerID=8YFLogxK

M3 - Article

VL - 151

SP - 4173

EP - 4182

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -