EPS (Erythroid Partner of SCL/tal-l) is a novel protein that interacts with the basic Helix aboutLoop-Helix (bHLH) family transcription factors SCL/tal-1 (Stem Cell Leukemia) and E12. EPS is expressed at the onset of yolk sac erythropoiesis in the developing mouse embryo, and enriched in the fetal liver, the site of definitive hematopoiesis, by E12.5. In adult mice, EPS is expressed in the spleen, lung and testis, as well as in all hematopoietic cells, including erythroid, megakaryocyte, myeloid and lymphoid cells. EPS acts as a transcriptional repressor when expressed in yeast, likely via an interaction with the co-repressors Sin3p and Rpd3p. Further studies demonstrated that over-expression of EPS in an erythroid cell line enhances GATA- 1 mediated terminal differentiation. Together these data suggest that EPS is a novel repressor of the SCLTE-protein heterodimers in hematopoietic cells that promotes erythroid cell differentiation. In this application, we propose to further characterize the role of this protein in hematopoiesis. Specifically, we plan to 1) Investigate the ability of EPS to repress transcription through histone deacetylases; 2) Analyze the key functional domains in EPS that are required for the promotion of erythroid cell differentiation, and identify EPS interacting proteins in these cells; and 3) Determine the role of EPS in vivo, by analysis of EPS-deficient embryos. Preliminary results indicate that EPS-deficient mice die in embryogenesis, as would be expected for an essential regulator of blood cell production. A more detailed assessment of the role of EPS in hematopoiesis will assist in our understanding of the role of lineage specific transcription factors in normal blood cell development, and may shed light into the mechanisms by which aberrant expression of these factors promote leukemia.
| Muntean, Andrew G; Pang, Liyan; Poncz, Mortimer et al. (2007) Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization. Blood 109:5199-207 |
| Xu, Y; Leung, C G; Lee, D C et al. (2006) MTB, the murine homolog of condensin II subunit CAP-G2, represses transcription and promotes erythroid cell differentiation. Leukemia 20:1261-9 |
| Crispino, John D (2005) GATA1 in normal and malignant hematopoiesis. Semin Cell Dev Biol 16:137-47 |
| Gurbuxani, Sandeep; Xu, Yanfei; Keerthivasan, Ganesan et al. (2005) Differential requirements for survivin in hematopoietic cell development. Proc Natl Acad Sci U S A 102:11480-5 |
| Smith, Erica D; Xu, Yanfei; Tomson, Brett N et al. (2004) More than blood, a novel gene required for mammalian postimplantation development. Mol Cell Biol 24:1168-73 |
