Yuan, H., Zhou, J., Deng, M., Zhang, Y., Chen, Y., Jin, Y., Zhu, J., Chen, S.J., The, H.D., Chen, Z., Liu, T.X., and Zhu, J. (2011) Sumoylation of CCAAT/enhancer-binding protein α promotes the biased primitive hematopoiesis of zebrafish. Blood. 117(26):7014-7020.
Hematopoiesis is evolutionarily conserved from zebrafish to mammals, including both primitive and definitive waves during embryogenesis. Primitive hematopoiesis is dominated by erythropoiesis with limited myelopoiesis. Protein sumoylation, a ubiquitination-like post-translational protein modification, is implicated in a variety of biochemical processes, notably transcriptional repression. We show that loss of SUMO paralogs triggers a sharp up-regulation of the myeloid-specific marker mpo and down-regulation of the erythroid-specific marker gata1 in myelo-erythroid progenitor cells (MPCs) in the intermediate cell mass (ICM) during primitive hematopoiesis. Accordingly, in transgenic zebrafish lines, hyposumoylation expands myelopoiesis at the expense of erythropoiesis. A SUMO-C/ebpα fusion restores the normal myelopoiesis/erythropoiesis balance, suggesting that sumoylation status of C/ebpα contributes to myelo-erythroid lineage determination. Our results thus implicate sumoylation in early lineage determination and point out the possible molecular mechanism underlying the puzzling biased primitive hematopoiesis in vertebrates.