Sumoylation of CCAAT/enhancer-binding protein alpha promotes the biased primitive hematopoiesis of zebrafish

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.