title: The 3'-Jα Region of the TCRα Locus Bears Gene Regulatory Activity in Thymic and Peripheral T Cells.
abstract: Much progress has been made in understanding the important cis-mediated controls on mouse TCRα gene function, including identification of the Eα enhancer and TCRα locus control region (LCR). Nevertheless, previous data have suggested that other cis-regulatory elements may reside in the locus outside of the Eα/LCR. Based on prior findings, we hypothesized the existence of gene regulatory elements in a 3.9-kb region 5' of the Cα exons. Using DNase hypersensitivity assays and TCRα BAC reporter transgenes in mice, we detected gene regulatory activity within this 3.9-kb region. This region is active in both thymic and peripheral T cells, and selectively affects upstream, but not downstream, gene expression. Together, these data indicate the existence of a novel cis-acting regulatory complex that contributes to TCRα transgene expression in vivo. The active chromatin sites we discovered within this region would remain in the locus after TCRα gene rearrangement, and thus may contribute to endogenous TCRα gene activity, particularly in peripheral T cells, where the Eα element has been found to be inactive.
authors.affiliation: Department of Biological Sciences, City University of New York, Hunter College, New York, New York, United States of America; Doctoral Program in Biology, City University of New York, Graduate Center, New York, New York, United States of America.
authors.forename: Martina
authors.initials: M
authors.lastname: Kučerová-Levisohn
authors.affiliation: Department of Biological Sciences, City University of New York, Hunter College, New York, New York, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knirr
authors.affiliation: Department of Biological Sciences, City University of New York, Hunter College, New York, New York, United States of America.
authors.forename: Rosa I
authors.initials: RI
authors.lastname: Mejia
authors.affiliation: Department of Biological Sciences, City University of New York, Hunter College, New York, New York, United States of America; Doctoral Program in Biology, City University of New York, Graduate Center, New York, New York, United States of America.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Ortiz
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics; D003850:Deoxyribonuclease I / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D056426:Genetic Loci; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D002843:Chromatin; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003850:Deoxyribonuclease I