title: Mammalian polycomb-mediated repression of Hox genes requires the essential spliceosomal protein Sf3b1.
abstract: Polycomb group (PcG) proteins are responsible for the stable repression of homeotic (Hox) genes by forming multimeric protein complexes. We show (1) physical interaction between components of the U2 small nuclear ribonucleoprotein particle (U2 snRNP), including Sf3b1 and PcG proteins Zfp144 and Rnf2; and (2) that Sf3b1 heterozygous mice exhibit skeletal transformations concomitant with ectopic Hox expressions. These alterations are enhanced by Zfp144 mutation but repressed by Mll mutation (a trithorax-group gene). Importantly, the levels of Sf3b1 in PcG complexes were decreased in Sf3b1-heterozygous embryos. These findings suggest that Sf3b1-PcG protein interaction is essential for true PcG-mediated repression of Hox genes.
authors.affiliation: Developmental Genetics Group, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Isono
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizutani-Koseki
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.forename: Marion S
authors.initials: MS
authors.lastname: Schmidt-Zachmann
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein; D010750:Phosphoproteins / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D011519:Proto-Oncogenes / Q000235:genetics; D000072260:RNA Splicing Factors; D012097:Repressor Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C066476:Pcgf6 protein, mouse; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D012097:Repressor Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; C491799:Sf3b1 protein, mouse; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases
references.citation: Mamm Genome. 2001 Mar;12(3):192-8
references.pmid: 11252167
references.citation: Development. 2001 May;128(9):1587-97
references.pmid: 11290297
references.citation: Nature. 2001 Aug 9;412(6847):651-5
references.pmid: 11493924
references.citation: Nature. 2001 Aug 9;412(6847):655-60
references.pmid: 11493925
references.citation: Mol Cell. 2001 Sep;8(3):545-56
references.pmid: 11583617
references.citation: Curr Opin Genet Dev. 2002 Apr;12(2):210-8
references.pmid: 11893495
references.citation: Development. 2002 Sep;129(18):4171-83
references.pmid: 12183370
references.citation: Mol Cell Biol. 2002 Nov;22(22):7919-28
references.pmid: 12391159
references.citation: Mol Cell. 2002 Nov;10(5):1119-28
references.pmid: 12453419
references.citation: J Cell Sci. 2003 Jan 15;116(Pt 2):335-43
references.pmid: 12482919
references.citation: Cell. 2003 Mar 7;112(5):599-606
references.pmid: 12628181
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13362-7
references.pmid: 14595010
references.citation: Mol Cell. 2004 Mar 26;13(6):887-93
references.pmid: 15053881
references.citation: Cell. 1992 Jan 24;68(2):283-302
references.pmid: 1346368
references.citation: Trends Genet. 1994 Oct;10(10):358-64
references.pmid: 7985240
references.citation: Nature. 1995 Nov 30;378(6556):505-8
references.pmid: 7477409
references.citation: Development. 1996 May;122(5):1513-22
references.pmid: 8625838
references.citation: Annu Rev Biochem. 1996;65:367-409
references.pmid: 8811184
references.citation: Curr Opin Genet Dev. 1997 Aug;7(4):488-94
references.pmid: 9309179
references.citation: Mol Biol Cell. 1998 Jan;9(1):143-60
references.pmid: 9436997
references.citation: Blood. 1998 Jul 1;92(1):108-17
references.pmid: 9639506
references.citation: Development. 1998 Sep;125(18):3543-51
references.pmid: 9716520
references.citation: Cell. 1999 Jul 9;98(1):37-46
references.pmid: 10412979
references.citation: Biochim Biophys Acta. 1999 Oct 6;1447(1):1-16
references.pmid: 10500238
references.citation: Dev Cell. 2004 Nov;7(5):663-76
references.pmid: 15525528
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14372-7
references.pmid: 10588712
references.citation: Nat Rev Mol Cell Biol. 2001 Jun;2(6):409-21
references.pmid: 11389465