| First Author | Pang L | Year | 2006 |
| Journal | Blood | Volume | 108 |
| Issue | 7 | Pages | 2198-206 |
| PubMed ID | 16757682 | Mgi Jnum | J:139476 |
| Mgi Id | MGI:3808108 | Doi | 10.1182/blood-2006-04-019760 |
| Citation | Pang L, et al. (2006) Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins. Blood 108(7):2198-206 |
| abstractText | Numerous megakaryocyte-specific genes contain signature Ets-binding sites in their regulatory regions. Fli-1 (friend leukemia integration 1), an Ets transcription factor, is required for the normal maturation of megakaryocytes and controls the expression of multiple megakaryocyte-specific genes. However, in Fli-1-/- mice, early megakaryopoiesis persists, and the expression of the early megakaryocyte-specific genes, alphaIIb and cMpl, is maintained, consistent with functional compensation by a related Ets factor(s). Here we identify the Ets protein GABPalpha (GA-binding protein alpha) as a regulator of early megakaryocyte-specific genes. Notably, GABPalpha preferentially occupies Ets elements of early megakaryocyte-specific genes in vitro and in vivo, whereas Fli-1 binds both early and late megakaryocyte-specific genes. Moreover, the ratio of GABPalpha/Fli-1 expression declines throughout megakaryocyte maturation. Consistent with this expression pattern, primary fetal liver-derived megakaryocytes from Fli-1-deficient murine embryos exhibit reduced expression of genes associated with late stages of maturation (glycoprotein [GP] Ibalpha, GPIX, and platelet factor 4 [PF4]), whereas GABPalpha-deficient megakaryocytes were mostly impaired in the expression of early megakaryocyte-specific genes (alphaIIb and cMpl). Finally, mechanistic experiments revealed that GABPalpha, like Fli-1, can impart transcriptional synergy between the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 (friend of GATA-1). In concert, these data reveal disparate, but overlapping, functions of Ets transcription factors at distinct stages of megakaryocyte maturation. |
