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Regulation of p110δ PI 3-Kinase Gene Expression

Kok, K; Nock, GE; Verrall, EA; Mitchell, MP; Hommes, DW; Peppelenbosch, MP; Vanhaesebroeck, B; (2009) Regulation of p110δ PI 3-Kinase Gene Expression. PLoS One , 4 (4) , Article e5145. 10.1371/journal.pone.0005145. Green open access

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Abstract

Background Despite an intense interest in the biological functions of the phosphoinositide 3-kinase (PI3K) signalling enzymes, little is known about the regulation of PI3K gene expression. This also applies to the leukocyte-enriched p110δ catalytic subunit of PI3K, an enzyme that has attracted widespread interest because of its role in immunity and allergy. Principal Findings We show that p110δ expression is mainly regulated at the transcriptional level. In fibroblasts, lymphocytes and myeloid cells, p110δ gene transcription appears to be constitutive and not subject to acute stimulation. 5′RACE experiments revealed that p110δ mRNA transcripts contain distinct upstream untranslated exons (named exon -1, -2a, -2b, -2c and -2d), which are located up to 81 kb upstream of the translational start codon in exon 1. The levels of all the different p110δ transcripts are higher in leukocytes compared to non-leukocytes, with the p110δ transcript containing exon -2a most abundantly expressed. We have identified a highly conserved transcription factor (TF) binding cluster in the p110δ gene which has enhanced promoter activity in leukocytes compared to non-leukocytes. In human, this TF cluster is located immediately upstream of exon -2a whilst in mouse, it is located within exon -2a. Conclusion This study identifies a conserved PIK3CD promoter region that may account for the predominant leukocyte expression of p110δ.

Type: Article
Title: Regulation of p110δ PI 3-Kinase Gene Expression
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0005145
Publisher version: http://dx.doi.org/10.1371/journal.pone.0005145
Language: English
Additional information: © 2009 Kok et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC2663053
Keywords: 5' Untranslated Regions, Animals, Base Sequence, Binding Sites, Cell Line, Class I Phosphatidylinositol 3-Kinases, DNA Methylation, Exons, Gene Expression Regulation, Enzymologic, Genes, Reporter, Histones, Humans, Isoenzymes, Leukocytes, Mice, Molecular Sequence Data, Phosphatidylinositol 3-Kinases, Promoter Regions, Genetic, RNA Stability, Sequence Analysis, DNA, Signal Transduction, Transcription Initiation Site
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/1419445
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