title: The DNA binding factor Hmg20b is a repressor of erythroid differentiation.
abstract: BACKGROUND
  In erythroblasts, the CoREST repressor complex is recruited to target promoters by the transcription factor Gfi1b, leading to repression of genes mainly involved in erythroid differentiation. Hmg20b is a subunit of CoREST, but its role in erythropoiesis has not yet been established.
  
  
  METHODS
  To study the role of Hmg20b in erythropoiesis, we performed knockdown experiments in a differentiation-competent mouse fetal liver cell line, and in primary mouse fetal liver cells. The effects on globin gene expression were determined. We used microarrays to investigate global gene expression changes induced by Hmg20b knockdown. Functional analysis was carried out on Hrasls3, an Hmg20b target gene.
  
  
  RESULTS
  We show that Hmg20b depletion induces spontaneous differentiation. To identify the target genes of Hmg20b, microarray analysis was performed on Hmg20b knockdown cells and controls. In line with its association to the CoREST complex, we found that 85% (527 out of 620) of the deregulated genes are up-regulated when Hmg20b levels are reduced. Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation. Among the consistently up-regulated targets were embryonic β-like globins and the phospholipase HRAS-like suppressor 3 (Hrasls3). We show that Hrasls3 expression is induced during erythroid differentiation and that knockdown of Hrasls3 inhibits terminal differentiation of proerythroblasts.
  
  
  CONCLUSIONS
  We conclude that Hmg20b acts as an inhibitor of erythroid differentiation, through the down-regulation of genes involved in differentiation such as Hrasls3, and activation of repressors of differentiation such as Gfi1b. In addition, Hmg20b suppresses embryonic β-like globins.
authors: Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
authors: Fatemehsadat
authors: F
authors: Esteghamat
authors: Thamar Bryn
authors: TB
authors: van Dijk
authors: Harald
authors: H
authors: Braun
authors: Sylvia
authors: S
authors: Dekker
authors: Reinier
authors: R
authors: van der Linden
authors: Jun
authors: J
authors: Hou
authors: Pavlos
authors: P
authors: Fanis
authors: Jeroen
authors: J
authors: Demmers
authors: Wilfred
authors: W
authors: van IJcken
authors: Zeliha
authors: Z
authors: Ozgür
authors: Rastislav
authors: R
authors: Horos
authors: Farzin
authors: F
authors: Pourfarzad
authors: Marieke
authors: M
authors: von Lindern
authors: Sjaak
authors: S
authors: Philipsen
references: Curr Biol. 2002 Jul 9;12(13):1076-85
references: 12121614
references: Mol Cell Biol. 1998 May;18(5):2462-73
references: 9566867
references: Blood. 2010 Apr 8;115(14):2784-95
references: 20124515
references: Oral Oncol. 2008 Apr;44(4):400-6
references: 17689134
references: Genomics. 1999 Sep 1;60(2):172-8
references: 10486208
references: Oncogene. 2001 Jun 21;20(28):3651-64
references: 11439328
references: Br J Haematol. 2005 Jul;130(1):121-9
references: 15982354
references: J Cell Biol. 1997 Feb 24;136(4):935-44
references: 9049257
references: Nat Biotechnol. 1997 Sep;15(9):871-5
references: 9306402
references: Invest New Drugs. 2010 Oct;28(5):575-86
references: 19636513
references: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7480-5
references: 12802011
references: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10458-63
references: 15240883
references: J Cell Sci. 2007 Apr 15;120(Pt 8):1393-404
references: 17374643
references: J Mol Neurosci. 2006;29(3):227-39
references: 17085781
references: Haematologica. 2010 Jan;95(1):36-46
references: 19773260
references: PLoS One. 2009 Dec 07;4(12):e7936
references: 19997604
references: Mol Cell. 2007 Aug 17;27(4):562-72
references: 17707228
references: Genes Dev. 2002 Feb 1;16(3):301-6
references: 11825872
references: J Cell Biol. 2004 Jan 19;164(2):175-84
references: 14734530
references: Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10141-6
references: 19497860
references: Protein Expr Purif. 2010 May;71(1):103-7
references: 20100577
references: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9873-8
references: 10449787
references: Methods Mol Biol. 2006;338:305-23
references: 16888367
references: Cancer Res. 2010 Jun 1;70(11):4402-11
references: 20460533
references: Cytogenet Cell Genet. 2000;88(1-2):62-7
references: 10773667
references: PLoS One. 2010 Apr 22;5(4):e10312
references: 20421987
references: Genes Dev. 2010 Apr 15;24(8):783-98
references: 20395365
references: Cell. 2006 Mar 24;124(6):1283-98
references: 16564017
references: J Lipid Res. 2009 Apr;50(4):685-93
references: 19047760
references: Methods. 2011 Feb;53(2):151-62
references: 20705139
references: IUBMB Life. 2009 Aug;61(8):800-30
references: 19621348
references: Genes Dev. 2010 Feb 1;24(3):277-89
references: 20123907
references: Mol Cell Biol. 1996 Aug;16(8):4024-34
references: 8754800
references: Hum Gene Ther. 2002 Jan 20;13(2):243-60
references: 11812281
references: J Lipid Res. 2008 Dec;49(12):2535-44
references: 18664718
references: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7420-5
references: 12032298
references: Blood. 2007 Mar 15;109(6):2356-64
references: 17095621
references: FASEB J. 2001 Jun;15(8):1442-4
references: 11387251
references: Stem Cells. 2009 Sep;27(9):2153-62
references: 19522008
references: Cell. 1982 Apr;28(4):907-19
references: 6954007
references: Curr Opin Hematol. 2006 Jul;13(4):203-8
references: 16755214