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Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control

Rothenberg, Ellen V. and Ungerbäck, Jonas and Champhekar, Ameya (2016) Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control. Advances in Immunology, 129 . pp. 109-174. ISSN 0065-2776. PMCID PMC4747653. doi:10.1016/

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T-lymphocyte development branches off from other lymphoid developmental programs through its requirement for sustained environmental signals through the Notch pathway. In the thymus, Notch signaling induces a succession of T-lineage regulatory factors that collectively create the T-cell identity through distinct steps. This process involves both the staged activation of T-cell identity genes and the staged repression of progenitor-cell-inherited regulatory genes once their roles in self-renewal and population expansion are no longer needed. With the recent characterization of innate lymphoid cells (ILCs) that share transcriptional regulation programs extensively with T-cell subsets, T-cell identity can increasingly be seen as defined in modular terms, as the processes selecting and actuating effector function are potentially detachable from the processes generating and selecting clonally unique T-cell receptor structures. The developmental pathways of different classes of T cells and ILCs are distinguished by the numbers of prerequisites of gene rearrangement, selection, and antigen contact before the cells gain access to nearly common regulatory mechanisms for choosing effector function. Here, the major classes of transcription factors that interact with Notch signals during T-lineage specification are discussed in terms of their roles in these programs, the evidence for their spectra of target genes at different stages, and their cross-regulatory and cooperative actions with each other. Specific topics include Notch modulation of PU.1 and GATA-3, PU.1-Notch competition, the relationship between PU.1 and GATA-3, and the roles of E proteins, Bcl11b, and GATA-3 in guiding acquisition of T-cell identity while avoiding redirection to an ILC fate.

Item Type:Article
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URLURL TypeDescription CentralArticle
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2016 Elsevier Inc. Available online 26 October 2015. The authors thank members of the Rothenberg group for discussion of the ideas presented here and for sharing relevant results before publication. Research in the Rothenberg lab was supported by grants from the USPHS, AI083514, AI095943, HD076915, and HL119102. J.U. was supported by the Swedish Research Council (Linköping University) and E.V.R. was supported by the Albert Billings Ruddock Professorship of Biology.
Funding AgencyGrant Number
Swedish Research CouncilUNSPECIFIED
Albert Billings Ruddock Professorship of BiologyUNSPECIFIED
Subject Keywords:T-cell development; Transcription factor; Gene regulation; Notch; GATA-3; PU.1; E2A
PubMed Central ID:PMC4747653
Record Number:CaltechAUTHORS:20160126-153717169
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Official Citation:Ellen V. Rothenberg, Jonas Ungerbäck, Ameya Champhekar, Chapter Four - Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control, In: Frederick W. Alt, Editor(s), Advances in Immunology, Academic Press, 2016, Volume 129, Pages 109-174, ISSN 0065-2776, ISBN 9780128047996, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63984
Deposited By: Tony Diaz
Deposited On:26 Jan 2016 23:58
Last Modified:10 Nov 2021 23:24

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