Journal
BLOOD
Volume 117, Issue 26, Pages 7014-7020Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-325712
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Funding
- National Natural Science Foundation of China [30525006, 31071290, 30525019]
- Shanghai Municipal Education Commission
- Centre National de la Recherche Scientifique and BNP Paribas
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Hematopoiesis is evolutionarily conserved from zebrafish to mammals, and this includes both primitive and definitive waves during embryogenesis. Primitive hematopoiesis is dominated by erythropoiesis with limited myelopoiesis. Protein sumoylation, a ubiquitination-like posttranslational protein modification, is implicated in a variety of biochemical processes, most notably in transcriptional repression. We show here that the loss of 6 small ubiquitin-related modifier (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. ASUMO-CCAAT/enhancer-binding protein alpha (SUMO-C/ebp alpha) fusion restores the normal myelopoiesis/erythropoiesis balance, suggesting that sumoylation status of C/ebp alpha contributes to myelo-erythroid lineage determination. Our results therefore implicate sumoylation in early lineage determination and reveal the possible molecular mechanism underlying the puzzling biased primitive hematopoiesis in vertebrates. (Blood. 2011;117(26):7014-7020)
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