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Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage

Anderson, Michele K. and Hernandez-Hoyos, Gabriela and Diamond, Rochelle A. and Rothenberg, Ellen V. (1999) Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development, 126 (14). pp. 3131-3148. ISSN 0950-1991. http://resolver.caltech.edu/CaltechAUTHORS:20120109-142434194

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Abstract

Ets family transcription factors control the expression of a large number of genes in hematopoietic cells. Here we show strikingly precise differential expression of a subset of these genes marking critical, early stages of mouse lymphocyte cell-type specification. Initially, the Ets family member factor Erg was identified during an arrayed cDNA library screen for genes encoding transcription factors expressed specifically during T cell lineage commitment. Multiparameter fluorescence-activated cell sorting for over a dozen cell surface markers was used to isolate 18 distinct primary-cell populations representing discrete T cell and B cell developmental stages, pluripotent lymphoid precursors, immature NK-like cells and myeloid hematopoietic cells. These populations were monitored for mRNA expression of the Erg, Ets-1, Ets-2, Fli-1, Tel, Elf-1, GABPalpha, PU.1 and Spi-B genes. The earliest stages in T cell differentiation show particularly dynamic Ets family gene regulation, with sharp transitions in expression correlating with specification and commitment events. Ets, Spi-B and PU.1 are expressed in these stages but not by later T-lineage cells. Erg is induced during T-lineage specification and then silenced permanently, after commitment, at the beta-selection checkpoint. Spi-B is transiently upregulated during commitment and then silenced at the same stage as Erg. T-lineage commitment itself is marked by repression of PU.1, a factor that regulates B-cell and myeloid genes. These results show that the set of Ets factors mobilized during T-lineage specification and commitment is different from the set that maintains T cell gene expression during thymocyte repertoire selection and in all classes of mature T cells.


Item Type:Article
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http://dev.biologists.org/content/126/14/3131.abstractPublisherUNSPECIFIED
Additional Information:© 1999 The Company of Biologists Limited. Accepted 27 April; published on WWW 21 June 1999.
Subject Keywords:T cell development; Ets family; gene expression; hematopoiesis
Record Number:CaltechAUTHORS:20120109-142434194
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120109-142434194
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:28717
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Jan 2012 19:16
Last Modified:26 Dec 2012 14:41

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