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Transcriptional Control and Deregulation

A novel transcript of the LMO2 gene, LMO2-c, is regulated by GATA-1 and PU.1 and encodes an antagonist of LMO2

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Abstract

Ectopic expression of LIM-only protein 2 (LMO2) in T-cells, as a result of chromosomal translocations or retroviral insertion, plays an important role in the onset of T-cell leukemias. Two transcripts of LMO2 gene (LMO2-a and LMO2-b) have been reported to encode a same 158-amino-acid protein. We have previously reported a novel transcript of human LMO2 gene (LMO2-c) encoding a 151-amino-acid protein, and defined its promoter region. In the present study, we investigated the regulation of the LMO2-c expression and the functions of LMO2-c. We found that LMO2-c expression is regulated by the cooperation of two essential hematopoietic transcription factors GATA-1 and PU.1 in various hematopoietic cell lines, suggesting an important functional role for LMO2-c in the hematopoietic system. More importantly, we demonstrated that LMO2-c acts as an antagonist of LMO2-a/b binding to its partners, therefore blocking the transactivation of LMO2-a/b on its target genes. These findings provide novel evidence to the functions of LMO2 gene in the hematopoietic system and leukemia.

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Acknowledgements

This work was supported by a grant from The Natural Sciences Foundation of Tianjin City (No. 05YFJMJC01800).

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Authors and Affiliations

  1. Laboratory of Molecular Medicine, Medical College, Nankai University, Tianjin, PR China

    Q Wang, M Zhang, X Wang, W Yuan & T Zhu

  2. Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY, USA

    D Chen

  3. Heinrich-Heine University, Institute of Human Genetics and Anthropology, Postfach, Duesseldorf, Germany

    B Royer-Pokora

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  1. Q Wang
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Correspondence to T Zhu.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Wang, Q., Zhang, M., Wang, X. et al. A novel transcript of the LMO2 gene, LMO2-c, is regulated by GATA-1 and PU.1 and encodes an antagonist of LMO2. Leukemia 21, 1015–1025 (2007). https://doi.org/10.1038/sj.leu.2404644

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