RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization

Nat Commun. 2012 Mar 6;3:717. doi: 10.1038/ncomms1704.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / biosynthesis
  • Cell Line
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Cytokinesis
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Megakaryocytes / cytology*
  • Megakaryocytes / metabolism
  • Mice
  • Mice, Knockout
  • Mitosis
  • Myosin Heavy Chains / biosynthesis
  • Myosin Heavy Chains / genetics*
  • Myosin Heavy Chains / metabolism
  • Nonmuscle Myosin Type IIB / biosynthesis
  • Nonmuscle Myosin Type IIB / genetics*
  • Nonmuscle Myosin Type IIB / metabolism
  • Polyploidy*
  • RNA Interference
  • RNA, Small Interfering

Substances

  • Antigens, CD34
  • Core Binding Factor Alpha 2 Subunit
  • Heterocyclic Compounds, 4 or More Rings
  • RNA, Small Interfering
  • Runx1 protein, mouse
  • blebbistatin
  • Nonmuscle Myosin Type IIB
  • nonmuscle myosin type IIB heavy chain
  • Myosin Heavy Chains