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Expression and Function of a Stem Cell Promoter for the Murine CBFα2 Gene: Distinct Roles and Regulation in Natural Killer and T Cell Development

Telfer, Janice C. and Rothenberg, Ellen V. (2001) Expression and Function of a Stem Cell Promoter for the Murine CBFα2 Gene: Distinct Roles and Regulation in Natural Killer and T Cell Development. Developmental Biology, 229 (2). pp. 363-382. ISSN 0012-1606. https://resolver.caltech.edu/CaltechAUTHORS:20170206-125607049

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Abstract

The Runt family transcription factor CBFα2 (AML1, PEBP2αB, or Runx1) is required by hematopoietic stem cells and expressed at high levels in T-lineage cells. In human T cells CBFα2 is usually transcribed from a different promoter (distal promoter) than in myeloid cells (proximal promoter), but the developmental and functional significance of this promoter switch has not been known. Here, we report that both coding and noncoding sequences of the distal 5′ end are highly conserved between the human and the murine genes, and the distal promoter is responsible for the overwhelming majority of CBFα2 expression in murine hematopoietic stem cells as well as in T cells. Distal promoter activity is maintained throughout T cell development and at lower levels in B cell development, but downregulated in natural killer cell development. The distal N-terminal isoform binds to functionally important regulatory sites from known target genes with two- to threefold higher affinity than the proximal N-terminal isoform. Neither full-length isoform alters growth of a myeloid cell line under nondifferentiating conditions, but the proximal isoform selectively delays mitotic arrest of the cell line under differentiating conditions, resulting in the generation of greater numbers of neutrophils.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1006/dbio.2000.9991DOIArticle
http://www.sciencedirect.com/science/article/pii/S0012160600999913PublisherArticle
ORCID:
AuthorORCID
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2000 Academic Press. Received for publication July 28, 2000; Revised October 13, 2000; Accepted October 23, 2000; Published online December 13, 2000. We thank several valued colleagues who contributed helpful reagents for this work: Dr. Elaine Spooncer, who provided the FDCP-mix cells; Dr. Peter Wong, who provided the BL3a cells; Dr. Schickwann Tsai, who provided the EML-C1 and BHK-MKL cells; Dr. Scott Hiebert, who generously sent us anti-AML1 antiserum; Dr. Luk van Parjis, who provided the bicistronic MSCV retroviral vector; Dr. Garry Nolan, who gave us the Phoenix packaging cells; and Shirley Pease, who donated the HM-1 ES cells. We are also glad to acknowledge the assistance of Rochelle Diamond and Pat Koen of the Flow Cytometry and Cell Sorting Facility and members of the Sequencing Facility, the Biopolymer Synthesis Facility, and the Protein–Peptide Microanalytical Laboratory, all at Caltech. This work was greatly aided by the advice and collaboration of Hua Wang, Dr. Michele Anderson, and Dr. Mary Yui in the Rothenberg group; by the help of Daniel Bolon, who isolated the CBFb cDNA clone; and by valuable comments and discussion from other members of the group throughout the work. J.C.T. gratefully acknowledges the support of an NIH Postdoctoral Training Grant. This research was supported in part by a grant from the USPHS, AI34041, and a grant from the State of California Tobacco-Related Disease Research Program, 4RT-0624.
Funders:
Funding AgencyGrant Number
NIHAI34041
California Tobacco-Related Disease Research Program4RT-0624
NIH Postdoctoral FellowshipUNSPECIFIED
Subject Keywords:CBFα2, PEBP2αB, AML1, Runx1; gene expression regulation, development; hematopoietic stem cells, growth and development
Issue or Number:2
Record Number:CaltechAUTHORS:20170206-125607049
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170206-125607049
Official Citation:Janice C. Telfer, Ellen V. Rothenberg, Expression and Function of a Stem Cell Promoter for the Murine CBFα2 Gene: Distinct Roles and Regulation in Natural Killer and T Cell Development, Developmental Biology, Volume 229, Issue 2, 15 January 2001, Pages 363-382, ISSN 0012-1606, http://dx.doi.org/10.1006/dbio.2000.9991. (//www.sciencedirect.com/science/article/pii/S0012160600999913)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74084
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Feb 2017 22:19
Last Modified:03 Oct 2019 16:34

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