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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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Blood, 15 June 2003, Vol. 101, No. 12, pp. 4757-4764

HEMATOPOIESIS

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

From the Division of Hematology/Oncology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, OH.

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. Although LMO2 has been shown to be critical for the formation of the erythroid cell lineage, the gene is also expressed in a number of nonerythroid tissues. In this report, we demonstrate that the more distal of the 2 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 proline and acidic amino acid–rich (PAR) domain. Although all 3 members of this family are produced in erythroid cells, only 2 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 because PAR proteins have not previously been implicated in this process.


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