DNA methylation contributes to tissue- and allele-specific expression of the T-cell differentiation marker RT6

Stefan Rothenburg, F. Koch-Nolte, H. G. Thiele, F. Haag

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We investigated the role of DNA methylation in gene regulation of the rat T-cell differentiation marker RT6. Analysis of the methylation status of various tissues revealed that the RT6 promoter was hypomethylated in RT6-expressing tissues, and methylated in nonexpressing ones. Remarkably, among RT6-nonexpressing tissues, the extent of methylated regions varied greatly between lymphatic tissues, where regions larger than 23 kb were methylated, and nonlymphatic tissues, where methylation was restricted to a 3- to 4-kb region surrounding the promoter. We have previously shown that cis-regulatory elements determine differential expression of the two RT6 alleles in a subpopulation of T cells. We now show that the RT6 alleles in these cells differed in their methylation status. The promoter region of the silent allele was methylated, while that of the transcribed allele was not. Upon treatment of RT6-nonexpressing thymoma cells with the methyltransferase inhibitor 5-azacytidine, RT6 expression was induced. In RT6 heterozygous hybridoma cells, expressing only one RT6 allele, induction of the silent, methylated RT6 allele was observed. Sensitivity of the RT6 promoter to DNA methylation was demonstrated by promoterspecific in vitro methylation, which inhibited RT6 promoter activity, while that of the SV40 promoter was not influenced. Our findings indicate that DNA methylation plays an important role in the control of monoallelic and tissue-specific RT6 expression.

Original languageEnglish (US)
Pages (from-to)231-241
Number of pages11
JournalImmunogenetics
Volume52
Issue number3-4
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Differentiation Antigens
DNA Methylation
Cell Differentiation
Alleles
T-Lymphocytes
Methylation
Genetic Promoter Regions
Azacitidine
Thymoma
Hybridomas
Methyltransferases
Lymphoid Tissue
Genes

Keywords

  • DNA methylation
  • Monoallelic expression
  • RT6
  • T-cell development
  • Tissue specificity

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

DNA methylation contributes to tissue- and allele-specific expression of the T-cell differentiation marker RT6. / Rothenburg, Stefan; Koch-Nolte, F.; Thiele, H. G.; Haag, F.

In: Immunogenetics, Vol. 52, No. 3-4, 2001, p. 231-241.

Research output: Contribution to journalArticle

@article{435114f8af5d4303b7a6cfd3cfba5bd7,
title = "DNA methylation contributes to tissue- and allele-specific expression of the T-cell differentiation marker RT6",
abstract = "We investigated the role of DNA methylation in gene regulation of the rat T-cell differentiation marker RT6. Analysis of the methylation status of various tissues revealed that the RT6 promoter was hypomethylated in RT6-expressing tissues, and methylated in nonexpressing ones. Remarkably, among RT6-nonexpressing tissues, the extent of methylated regions varied greatly between lymphatic tissues, where regions larger than 23 kb were methylated, and nonlymphatic tissues, where methylation was restricted to a 3- to 4-kb region surrounding the promoter. We have previously shown that cis-regulatory elements determine differential expression of the two RT6 alleles in a subpopulation of T cells. We now show that the RT6 alleles in these cells differed in their methylation status. The promoter region of the silent allele was methylated, while that of the transcribed allele was not. Upon treatment of RT6-nonexpressing thymoma cells with the methyltransferase inhibitor 5-azacytidine, RT6 expression was induced. In RT6 heterozygous hybridoma cells, expressing only one RT6 allele, induction of the silent, methylated RT6 allele was observed. Sensitivity of the RT6 promoter to DNA methylation was demonstrated by promoterspecific in vitro methylation, which inhibited RT6 promoter activity, while that of the SV40 promoter was not influenced. Our findings indicate that DNA methylation plays an important role in the control of monoallelic and tissue-specific RT6 expression.",
keywords = "DNA methylation, Monoallelic expression, RT6, T-cell development, Tissue specificity",
author = "Stefan Rothenburg and F. Koch-Nolte and Thiele, {H. G.} and F. Haag",
year = "2001",
doi = "10.1007/s002510000267",
language = "English (US)",
volume = "52",
pages = "231--241",
journal = "Immunogenetics",
issn = "0093-7711",
publisher = "Springer Verlag",
number = "3-4",

}

TY - JOUR

T1 - DNA methylation contributes to tissue- and allele-specific expression of the T-cell differentiation marker RT6

AU - Rothenburg, Stefan

AU - Koch-Nolte, F.

AU - Thiele, H. G.

AU - Haag, F.

PY - 2001

Y1 - 2001

N2 - We investigated the role of DNA methylation in gene regulation of the rat T-cell differentiation marker RT6. Analysis of the methylation status of various tissues revealed that the RT6 promoter was hypomethylated in RT6-expressing tissues, and methylated in nonexpressing ones. Remarkably, among RT6-nonexpressing tissues, the extent of methylated regions varied greatly between lymphatic tissues, where regions larger than 23 kb were methylated, and nonlymphatic tissues, where methylation was restricted to a 3- to 4-kb region surrounding the promoter. We have previously shown that cis-regulatory elements determine differential expression of the two RT6 alleles in a subpopulation of T cells. We now show that the RT6 alleles in these cells differed in their methylation status. The promoter region of the silent allele was methylated, while that of the transcribed allele was not. Upon treatment of RT6-nonexpressing thymoma cells with the methyltransferase inhibitor 5-azacytidine, RT6 expression was induced. In RT6 heterozygous hybridoma cells, expressing only one RT6 allele, induction of the silent, methylated RT6 allele was observed. Sensitivity of the RT6 promoter to DNA methylation was demonstrated by promoterspecific in vitro methylation, which inhibited RT6 promoter activity, while that of the SV40 promoter was not influenced. Our findings indicate that DNA methylation plays an important role in the control of monoallelic and tissue-specific RT6 expression.

AB - We investigated the role of DNA methylation in gene regulation of the rat T-cell differentiation marker RT6. Analysis of the methylation status of various tissues revealed that the RT6 promoter was hypomethylated in RT6-expressing tissues, and methylated in nonexpressing ones. Remarkably, among RT6-nonexpressing tissues, the extent of methylated regions varied greatly between lymphatic tissues, where regions larger than 23 kb were methylated, and nonlymphatic tissues, where methylation was restricted to a 3- to 4-kb region surrounding the promoter. We have previously shown that cis-regulatory elements determine differential expression of the two RT6 alleles in a subpopulation of T cells. We now show that the RT6 alleles in these cells differed in their methylation status. The promoter region of the silent allele was methylated, while that of the transcribed allele was not. Upon treatment of RT6-nonexpressing thymoma cells with the methyltransferase inhibitor 5-azacytidine, RT6 expression was induced. In RT6 heterozygous hybridoma cells, expressing only one RT6 allele, induction of the silent, methylated RT6 allele was observed. Sensitivity of the RT6 promoter to DNA methylation was demonstrated by promoterspecific in vitro methylation, which inhibited RT6 promoter activity, while that of the SV40 promoter was not influenced. Our findings indicate that DNA methylation plays an important role in the control of monoallelic and tissue-specific RT6 expression.

KW - DNA methylation

KW - Monoallelic expression

KW - RT6

KW - T-cell development

KW - Tissue specificity

UR - http://www.scopus.com/inward/record.url?scp=0035134563&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035134563&partnerID=8YFLogxK

U2 - 10.1007/s002510000267

DO - 10.1007/s002510000267

M3 - Article

C2 - 11220625

AN - SCOPUS:0035134563

VL - 52

SP - 231

EP - 241

JO - Immunogenetics

JF - Immunogenetics

SN - 0093-7711

IS - 3-4

ER -