Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs

The Journal of Clinical Investigation
Sakie OhmuraJames Douglas Engel

Abstract

The transcription factor GATA3 is essential for the genesis and maturation of the T cell lineage, and GATA3 dysregulation has pathological consequences. Previous studies have shown that GATA3 function in T cell development is regulated by multiple signaling pathways and that the Notch nuclear effector, RBP-J, binds specifically to the Gata3 promoter. We previously identified a T cell-specific Gata3 enhancer (Tce1) lying 280 kb downstream from the structural gene and demonstrated in transgenic mice that Tce1 promoted T lymphocyte-specific transcription of reporter genes throughout T cell development; however, it was not clear if Tce1 is required for Gata3 transcription in vivo. Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte-specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell-regulatory e...Continue Reading

References

Sep 8, 1995·Science·R KühnK Rajewsky
Jan 12, 1999·Developmental Biology·G LakshmananJ D Engel
Aug 10, 2000·Nature·H Van EschK Devriendt
Jul 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·M C NawijnR W Hendriks
Oct 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·T TaghonG Leclercq
Apr 24, 2002·Developmental Biology·Jennifer C J ChenDavid J Goldhamer
Jul 23, 2003·Immunity·Gabriela Hernández-HoyosJose Alberola-Ila
Feb 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sung-Yun PaiI-Cheng Ho
Jun 25, 2004·Nucleic Acids Research·Gabriela G Loots, Ivan Ovcharenko
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sonja HöflingerMeinrad Busslinger
Oct 12, 2004·Nature Immunology·Jinfang ZhuWilliam E Paul
Jan 6, 2005·The American Journal of Pathology·Cigdem AtayarAnke van den Berg
Jan 8, 2005·The Journal of Allergy and Clinical Immunology·Maritta PykäläinenRiitta Lahesmaa
Mar 18, 2005·Annual Review of Immunology·Ellen V Rothenberg, Tom Taghon
Mar 18, 2005·Annual Review of Immunology·Ivan MaillardWarren S Pear
Jun 14, 2005·Nature Immunology·Arivazhagan SambandamAvinash Bhandoola
Feb 2, 2006·Immunological Reviews·Elizabeth-Sharon David-FungEllen V Rothenberg
Oct 3, 2006·Nature Immunology·Christian A J VosshenrichJames P Di Santo
Oct 19, 2006·Developmental Biology·Susan L HasegawaKim-Chew Lim
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jason WojciechowskiYuan Zhuang
Jun 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·C Chace TydellEllen V Rothenberg
Jul 21, 2007·The EMBO Journal·Diane MauriceKathleen Weston

❮ Previous
Next ❯

Citations

Apr 23, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Joseph M MianoCharles J Lowenstein
Aug 22, 2018·Molecular and Cellular Biology·Takashi MoriguchiJames Douglas Engel
May 20, 2020·Nature Communications·Chen-Hao ChenX Shirley Liu
Sep 13, 2020·Nature Reviews. Immunology·Hiroyuki Hosokawa, Ellen V Rothenberg
Jul 31, 2019·Nature Immunology·Christelle HarlyAvinash Bhandoola
Apr 6, 2018·Scientific Reports·Tomonori HosoyaJames Douglas Engel
Sep 25, 2020·Immunology and Cell Biology·Wing Fuk ChanRhys S Allan
Jun 24, 2021·The Journal of Experimental Medicine·Rui YangFederica Sallusto
Aug 7, 2021·Proceedings of the National Academy of Sciences of the United States of America·Darshan N KasalAlbert Bendelac

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
PCR
ChIP
ChIP-seq
Flow Cytometry

Software Mentioned

rVISTA
FlowJo

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.