Redundant and unique roles of two enhancer elements in the TCRgamma locus in gene regulation and gammadelta T cell development

Immunity
Na XiongDavid H Raulet

Abstract

Many mammalian genes, including those encoding antigen receptors, contain more than one enhancer element. Deleting one element often does not prevent expression, but functional redundancy has never been directly demonstrated by gene targeting of multiple elements. We demonstrate that simultaneous deletion of two enhancer/LCR-like elements in the TCR Cgamma1 cluster, HsA and 3'E(Cgamma1), severely diminishes TCRgamma transcription, selectively impairs development of gammadelta thymocyte subsets, but only modestly reduces TCRgamma gene rearrangement, while deletion of each element separately has little effect. In contrast to these results in thymocytes, deletion of HsA alone reduces transcription of one Vgamma gene specifically in peripheral gammadelta T cells. Thus, the two elements exhibit functional redundancy in thymocytes but also have unique functions in other settings.

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Citations

Oct 5, 2010·Archivum Immunologiae Et Therapiae Experimentalis·Michael L SikesJustin M Bradshaw
Mar 17, 2004·Current Opinion in Immunology·Joonsoo Kang, Sandy D Der
Apr 2, 2008·The Journal of Experimental Medicine·Na XiongDavid H Raulet
Aug 25, 2010·The Journal of Experimental Medicine·Pingxin LiYanming Wang
Jan 17, 2008·Genes & Development·Chris J CretekosRichard R Behringer
Dec 24, 2003·Proceedings of the National Academy of Sciences of the United States of America·Na XiongDavid H Raulet
Dec 22, 2015·Current Biology : CB·Enrico CannavòEileen E M Furlong
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