Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1)

R J Holt, Y M Zhang, A Binia, Anna L Dixon, C Vandiedonck, W O Cookson, J C Knight, M F Moffatt

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Asthma is a common, chronic inflammatory airway disease of major public health importance with multiple genetic determinants. Previously, we found by positional cloning that PHD finger protein 11 (PHF11) on chromosome 13q14 modifies serum immunoglobulin E (IgE) concentrations and asthma susceptibility. No coding variants in PHF11 were identified.

Objective: Here we investigate the 3 single nucleotide polymorphisms (SNPs) in this gene most significantly associated with total serum IgE levels-rs3765526, rs9526569, and rs1046295-for a role in transcription factor binding.

Methods: We used electrophoretic mobility shift assays to examine the effect of the 3 SNPs on transcription factor binding in 3 cell lines relevant to asthma pathogenesis. Relative preferential expression of alleles was investigated by using the allelotyping method.

Results: Electrophoretic mobility shift assays show that rs1046295 modulates allele-specific binding by the octamer-binding transcription factor 1 (Oct-1). Analysis of the relative expression levels of the 2 alleles of this SNP in heterozygous individuals showed a modest, but highly significant (P = 6.5 x 10(-16)), preferential expression of the A allele consistent with a functional role for rs1046295.

Conclusion: These results suggest a mechanism by which rs1046295 may act as a regulatory variant modulating transcription at this locus and altering asthma susceptibility.

Original languageEnglish
Pages (from-to)1054-U322
JournalJournal of Allergy and Clinical Immunology
Volume127
Issue number4
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Octamer Transcription Factor-1
Fingers
Asthma
Alleles
Single Nucleotide Polymorphism
Electrophoretic Mobility Shift Assay
Immunoglobulin E
Proteins
Transcription Factors
Chromosomes, Human, Pair 11
Serum
Organism Cloning
Public Health
Cell Line
Genes

Keywords

  • electrophoretic mobility shift assay
  • rs1046295
  • IgE
  • gene expression
  • PHF11
  • Oct-1
  • asthma genetics

Cite this

Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1). / Holt, R J; Zhang, Y M; Binia, A; Dixon, Anna L; Vandiedonck, C; Cookson, W O; Knight, J C; Moffatt, M F.

In: Journal of Allergy and Clinical Immunology, Vol. 127, No. 4, 04.2011, p. 1054-U322.

Research output: Contribution to journalArticle

Holt, R J ; Zhang, Y M ; Binia, A ; Dixon, Anna L ; Vandiedonck, C ; Cookson, W O ; Knight, J C ; Moffatt, M F. / Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1). In: Journal of Allergy and Clinical Immunology. 2011 ; Vol. 127, No. 4. pp. 1054-U322.
@article{3153640d64944785b7505e9ad98ba34f,
title = "Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1)",
abstract = "Background: Asthma is a common, chronic inflammatory airway disease of major public health importance with multiple genetic determinants. Previously, we found by positional cloning that PHD finger protein 11 (PHF11) on chromosome 13q14 modifies serum immunoglobulin E (IgE) concentrations and asthma susceptibility. No coding variants in PHF11 were identified. Objective: Here we investigate the 3 single nucleotide polymorphisms (SNPs) in this gene most significantly associated with total serum IgE levels-rs3765526, rs9526569, and rs1046295-for a role in transcription factor binding. Methods: We used electrophoretic mobility shift assays to examine the effect of the 3 SNPs on transcription factor binding in 3 cell lines relevant to asthma pathogenesis. Relative preferential expression of alleles was investigated by using the allelotyping method. Results: Electrophoretic mobility shift assays show that rs1046295 modulates allele-specific binding by the octamer-binding transcription factor 1 (Oct-1). Analysis of the relative expression levels of the 2 alleles of this SNP in heterozygous individuals showed a modest, but highly significant (P = 6.5 x 10(-16)), preferential expression of the A allele consistent with a functional role for rs1046295. Conclusion: These results suggest a mechanism by which rs1046295 may act as a regulatory variant modulating transcription at this locus and altering asthma susceptibility.",
keywords = "electrophoretic mobility shift assay, rs1046295, IgE, gene expression, PHF11, Oct-1, asthma genetics",
author = "Holt, {R J} and Zhang, {Y M} and A Binia and Dixon, {Anna L} and C Vandiedonck and Cookson, {W O} and Knight, {J C} and Moffatt, {M F}",
year = "2011",
month = "4",
doi = "10.1016/j.jaci.2010.12.015",
language = "English",
volume = "127",
pages = "1054--U322",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1)

AU - Holt, R J

AU - Zhang, Y M

AU - Binia, A

AU - Dixon, Anna L

AU - Vandiedonck, C

AU - Cookson, W O

AU - Knight, J C

AU - Moffatt, M F

PY - 2011/4

Y1 - 2011/4

N2 - Background: Asthma is a common, chronic inflammatory airway disease of major public health importance with multiple genetic determinants. Previously, we found by positional cloning that PHD finger protein 11 (PHF11) on chromosome 13q14 modifies serum immunoglobulin E (IgE) concentrations and asthma susceptibility. No coding variants in PHF11 were identified. Objective: Here we investigate the 3 single nucleotide polymorphisms (SNPs) in this gene most significantly associated with total serum IgE levels-rs3765526, rs9526569, and rs1046295-for a role in transcription factor binding. Methods: We used electrophoretic mobility shift assays to examine the effect of the 3 SNPs on transcription factor binding in 3 cell lines relevant to asthma pathogenesis. Relative preferential expression of alleles was investigated by using the allelotyping method. Results: Electrophoretic mobility shift assays show that rs1046295 modulates allele-specific binding by the octamer-binding transcription factor 1 (Oct-1). Analysis of the relative expression levels of the 2 alleles of this SNP in heterozygous individuals showed a modest, but highly significant (P = 6.5 x 10(-16)), preferential expression of the A allele consistent with a functional role for rs1046295. Conclusion: These results suggest a mechanism by which rs1046295 may act as a regulatory variant modulating transcription at this locus and altering asthma susceptibility.

AB - Background: Asthma is a common, chronic inflammatory airway disease of major public health importance with multiple genetic determinants. Previously, we found by positional cloning that PHD finger protein 11 (PHF11) on chromosome 13q14 modifies serum immunoglobulin E (IgE) concentrations and asthma susceptibility. No coding variants in PHF11 were identified. Objective: Here we investigate the 3 single nucleotide polymorphisms (SNPs) in this gene most significantly associated with total serum IgE levels-rs3765526, rs9526569, and rs1046295-for a role in transcription factor binding. Methods: We used electrophoretic mobility shift assays to examine the effect of the 3 SNPs on transcription factor binding in 3 cell lines relevant to asthma pathogenesis. Relative preferential expression of alleles was investigated by using the allelotyping method. Results: Electrophoretic mobility shift assays show that rs1046295 modulates allele-specific binding by the octamer-binding transcription factor 1 (Oct-1). Analysis of the relative expression levels of the 2 alleles of this SNP in heterozygous individuals showed a modest, but highly significant (P = 6.5 x 10(-16)), preferential expression of the A allele consistent with a functional role for rs1046295. Conclusion: These results suggest a mechanism by which rs1046295 may act as a regulatory variant modulating transcription at this locus and altering asthma susceptibility.

KW - electrophoretic mobility shift assay

KW - rs1046295

KW - IgE

KW - gene expression

KW - PHF11

KW - Oct-1

KW - asthma genetics

UR - http://www.scopus.com/inward/record.url?scp=79953668692&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1016/j.jaci.2010.12.015

U2 - 10.1016/j.jaci.2010.12.015

DO - 10.1016/j.jaci.2010.12.015

M3 - Article

VL - 127

SP - 1054-U322

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 4

ER -