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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-09-2702.

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2002-09-2702v1
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Submitted September 4, 2002
Accepted February 12, 2003

A PAR domain transcription factor is involved in the expression from a hematopoietic-specific promoter for the human LMO2 gene

Scott C Crable and Kathleen P Anderson*

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

* Corresponding author; email: kathleen.anderson{at}chmcc.org.

The transcription factor LMO2 is believed to exert its effect through the formation of protein-protein interactions with other DNA-binding factors such as GATA-1 and TAL1. While LMO2 has been shown to be critical for the formation of the erythroid cell lineage, the gene is also expressed in a number of non-erythroid tissues. In this report, we demonstrate that the more distal of the two promoters for the LMO2 gene is highly restricted in its pattern of expression, directing the hematopoietic-specific expression of this gene. Deletion and mutation analyses have identified a critical cis element in the first untranslated exon of the gene. This element is a consensus binding site for a small family of basic leucine zipper proteins containing a PAR domain. While all three members of this family are produced in erythroid cells, only two of these proteins, thyrotroph embryonic factor and hepatic leukemia factor, can activate transcription from this LMO2 promoter element. These findings represent a novel mechanism in erythroid gene regulation since PAR proteins have not previously been implicated in this process.


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