@entity1092 ( @entity2052 ) exhibits important pharmacological properties but has been reported to trigger side effects, notably on the hematological system. We previously reported that @entity2052 affects hematopoietic homeostasis by inhibiting erythroid differentiation and promoting myeloid and megakaryocyte differentiation. Here, we analyzed the effect of @entity2052 on regulatory factors involved in erythro-megakaryocytic differentiation pathways, including transcription factors and microRNAs (miRs). We demonstrate that @entity2052 inhibited erythroid differentiation in @entity1307 ( @entity1307 )-stimulated TF1 @entity1778 cells and @entity2280 (+)/hematopoietic stem cells (HSCs) and in @entity8256 -(Acla)-treated K562 cells. @entity68237 gene expression was decreased in all erythroid and megakaryocyte models in correlation with @entity3421 inhibition. In @entity1307 -stimulated @entity2280 (+)/HSCs, @entity2052 induced the expression of the ETS family transcription factors @entity7764 , @entity12136 , @entity28588 , @entity21468 and @entity12627 , which are all known to be negative regulators of erythropoiesis, while it promoted the megakaryocytic pathway. @entity7764 and @entity12136 expression were induced in correlation with @entity10015 inhibition; however, the @entity3421 / @entity7764 interaction was promoted. Using megakaryoblastic Meg-01 cells, we demonstrated that @entity2052 induced megakaryocyte morphological features and @entity1428 expression. @entity12627 and @entity4449 expression were increased in correlation with a decrease in @entity5316 mRNA expression, suggesting megakaryocyte differentiation. Finally, by using @entity2148 and the Class I HDACi @entity12232 , we validated that the well-described HDACi activity of @entity2052 is not required in the inhibitory effect on erythropoiesis. Overall, this report shows that @entity2052 modulates the erythro-megakaryocytic differentiation program through regulatory micro-networks involving GATA and ETS transcription factors and miRNAs, notably the @entity3421 / @entity41669 /451 axis.

XXXX regulates erythro-megakaryocytic differentiation through the modulation of transcription factors and microRNA regulatory micro-networks.

@entity4449 :: ('407018', 'Gene') :: ['miR-27a'] @entity12136 :: ('2113', 'Gene') :: ['ETS-1'] @entity28588 :: ('2551', 'Gene') :: ['GABP-a'] @entity10015 :: ('406947', 'Gene') :: ['miR-155'] @entity8256 :: ('MESH:C011157', 'Chemical') :: ['aclacinomycin'] @entity1092 :: ('MESH:D014635', 'Chemical') :: ['Valproic acid'] @entity3421 :: ('2623', 'Gene') :: ['GATA-1'] @entity1307 :: ('2056', 'Gene') :: ['erythropoietin', 'Epo'] @entity12232 :: ('MESH:C118739', 'Chemical') :: ['MS-275'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemia'] @entity2052 :: ('CHEBI:39867', 'Chemical') :: ['VPA'] @entity1428 :: ('3690', 'Gene') :: ['CD61'] @entity7764 :: ('6688', 'Gene') :: ['PU.1'] @entity68237 :: ('406936;574411', 'Gene') :: ['Mir-144/451'] @entity21468 :: ('2313', 'Gene') :: ['Fli-1'] @entity2148 :: ('MESH:C004651', 'Chemical') :: ['valpromide'] @entity2280 :: ('947', 'Gene') :: ['CD34'] @entity12627 :: ('2624', 'Gene') :: ['GATA-2'] @entity5316 :: ('861', 'Gene') :: ['RUNX1'] @entity41669 :: ('406936', 'Gene') :: ['miR-144']
@entity1092 :: (MESH:D014635,Chemical) :: ['Valproic acid']
