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Elements of Transcription Factor Network Design for T-Lineage Specification

Rothenberg, Ellen V. and Anderson, Michele K. (2002) Elements of Transcription Factor Network Design for T-Lineage Specification. Developmental Biology, 246 (1). pp. 29-44. ISSN 0012-1606. doi:10.1006/dbio.2002.0667. https://resolver.caltech.edu/CaltechAUTHORS:20170206-110847853

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Abstract

The complex spectrum of cell types produced in mammalian hematopoiesis can be understood as the output of highly combinatorial transcription factor action. The generation of multiple diverse combinations of transcription factors from the common starting state of the hematopoietic stem cell must be explained through the cross-regulatory interactions of these transcription factors at several levels. Here, the operation of such a network is addressed through a focus on murine T cell development, where we have recently established regulatory linkages between GATA-3 and PU.1 and multiple other factors essential to this differentiation pathway. The action of both essential/rate-limiting factors and factors with effects that shift qualitatively with dose and time of action can be traced through the regulatory interaction network. Hypothetical models are proposed to indicate the network nodes that are differentially activated in normal T cell lineage progression and in cells diverted to other potential fates.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1006/dbio.2002.0667DOIArticle
http://www.sciencedirect.com/science/article/pii/S0012160602906676PublisherArticle
ORCID:
AuthorORCID
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2002 Elsevier Science. Received for publication January 24, 2002; Revised March 25, 2002; Accepted March 25, 2002. We thank Drs. Meinrad Busslinger (IMP, University of Vienna), Cornelis Murre (University of California, San Diego), Harinder Singh (University of Chicago), and Irving Weissman (Stanford University) for stimulating and challenging discussions; our colleagues Eric Davidson and Jonathan Rast for valuable criticism and insightful advice throughout many stages of this work; and other members of the Rothenberg group for their experimental results, interpretations, and collegial generosity that have made this analysis possible. Work from the authors’ lab described here was supported by grants from the National Institutes of Health (CA90233), the National Science Foundation (MCB-9983129), and initial consortium funding from the Stowers Institute for Medical Research.
Funders:
Funding AgencyGrant Number
NIHCA90233
NSFMCB-9983129
Stowers Institute for Medical ResearchUNSPECIFIED
Subject Keywords:T cell development; hematopoiesis; GATA-3; PU.1; transcriptional network; combinatorial regulation; dose dependent regulation; lineage choice
Issue or Number:1
DOI:10.1006/dbio.2002.0667
Record Number:CaltechAUTHORS:20170206-110847853
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170206-110847853
Official Citation:Ellen V. Rothenberg, Michele K. Anderson, Elements of Transcription Factor Network Design for T-Lineage Specification, Developmental Biology, Volume 246, Issue 1, 1 June 2002, Pages 29-44, ISSN 0012-1606, http://dx.doi.org/10.1006/dbio.2002.0667. (//www.sciencedirect.com/science/article/pii/S0012160602906676)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74076
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Feb 2017 20:28
Last Modified:11 Nov 2021 05:24

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