NDLI: Lymphoid enhancer binding factor 1 regulates transcription through gene looping.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yun, Kangsun Im, Sin-Hyeog So, Jae-Seon Jash, Arijita
Description	Author Affiliation: Yun K ( Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.)
Abstract	Efficient transcription depends upon efficient physical and functional interactions between transcriptosome complexes and DNA. We have previously shown that IL-1beta-induced lymphoid enhancer binding factor 1 (Lef1) regulates the transcription of its target genes COX2 and MMP13 in mouse chondrocytes by binding to the Lef1 binding sites located in the 3' region. In this study, we investigated how the 3' region-bound Lef1 regulates expression of target genes. IL-1beta stimulation induced gene looping in COX2 and MMP13 genomic loci, which is mediated by the physical interaction of Lef1 with its binding partners, including beta-catenin, AP-1, and NF-kappaB. As shown by chromosome conformation capture (3C) assay, the 5' and 3' genomic regions of these genes were juxtaposed in an IL-1beta-stimulation dependent manner. Lef1 played a pivotal role in this gene looping; Lef1 knockdown decreased the incidence of gene looping, while Lef1 overexpression induced it. Physical interactions between the 3' region-bound Lef1 and promoter-bound transcription factors AP-1 or NF-kappaB in COX2 and MMP13, respectively, were increased upon stimulation, leading to synergistic up-regulation of gene expression. Knockdown of RelA or c-Jun decreased the formation of gene loop and down-regulated cyclooxygenase 2 (COX2) or matrix metalloproteinase 13 (MMP13) transcription levels. However, overexpression of RelA or c-Jun along with Lef1 increased the looping and their expression levels. Our results indicate a novel function of Lef1, as a mediator of gene looping between 5' and 3' regions. Gene looping may serve to delineate the transcription unit in the inducible gene transcription of mammalian cells.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cyclooxygenase 2 Metabolism Gene Expression Regulation Lymphoid Enhancer-binding Factor 1 Matrix Metalloproteinase 13 Nf-kappa B Animals Cells, Cultured Chondrocytes Genetics Chemistry Gene Knockdown Techniques Genes, Jun Interleukin-1beta Pharmacology Drug Effects Mice Agonists Nucleic Acid Conformation Rna, Small Interfering Transcription Factor Ap-1 Transcription Factor Rela Transcription, Genetic Beta Catenin Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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