title: RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization.
abstract: Megakaryocytes are unique mammalian cells that undergo polyploidization (endomitosis) during differentiation, leading to an increase in cell size and protein production that precedes platelet production. Recent evidence demonstrates that endomitosis is a consequence of a late failure in cytokinesis associated with a contractile ring defect. Here we show that the non-muscle myosin IIB heavy chain (MYH10) is expressed in immature megakaryocytes and specifically localizes in the contractile ring. MYH10 downmodulation by short hairpin RNA increases polyploidization by inhibiting the return of 4N cells to 2N, but other regulators, such as of the G1/S transition, might regulate further polyploidization of the 4N cells. Conversely, re-expression of MYH10 in the megakaryocytes prevents polyploidization and the transition of 2N to 4N cells. During polyploidization, MYH10 expression is repressed by the major megakaryocyte transcription factor RUNX1. Thus, RUNX1-mediated silencing of MYH10 is required for the switch from mitosis to endomitosis, linking polyploidization with megakaryocyte differentiation.
authors.affiliation: INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France.
authors.forename: Larissa
authors.initials: L
authors.lastname: Lordier
authors.forename: Dominique
authors.initials: D
authors.lastname: Bluteau
authors.forename: Abdelali
authors.initials: A
authors.lastname: Jalil
authors.forename: Céline
authors.initials: C
authors.lastname: Legrand
authors.forename: Jiajia
authors.initials: J
authors.lastname: Pan
authors.forename: Philippe
authors.initials: P
authors.lastname: Rameau
authors.forename: Dima
authors.initials: D
authors.lastname: Jouni
authors.forename: Olivier
authors.initials: O
authors.lastname: Bluteau
authors.forename: Thomas
authors.initials: T
authors.lastname: Mercher
authors.forename: Catherine
authors.initials: C
authors.lastname: Leon
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.forename: Najet
authors.initials: N
authors.lastname: Debili
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Hana
authors.initials: H
authors.lastname: Raslova
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D024501:Nonmuscle Myosin Type IIB / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011123:Polyploidy; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D018952:Antigens, CD34; D050676:Core Binding Factor Alpha 2 Subunit; D006576:Heterocyclic Compounds, 4 or More Rings; D034741:RNA, Small Interfering; C493726:Runx1 protein, mouse; C472645:blebbistatin; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains