title: Endogenous retroviruses function as species-specific enhancer elements in the placenta.
abstract: The mammalian placenta is remarkably distinct between species, suggesting a history of rapid evolutionary diversification. To gain insight into the molecular drivers of placental evolution, we compared biochemically predicted enhancers in mouse and rat trophoblast stem cells (TSCs) and found that species-specific enhancers are highly enriched for endogenous retroviruses (ERVs) on a genome-wide level. One of these ERV families, RLTR13D5, contributes hundreds of mouse-specific histone H3 lysine 4 monomethylation (H3K4me1)- and histone H3 lysine 27 acetylation (H3K27ac)-defined enhancers that functionally bind Cdx2, Eomes and Elf5-core factors that define the TSC regulatory network. Furthermore, we show that RLTR13D5 is capable of driving gene expression in rat placental cells. Analysis in other tissues shows that species-specific ERV enhancer activity is generally restricted to hypomethylated tissues, suggesting that tissues permissive for ERV activity gain access to an otherwise silenced source of regulatory variation. Overall, our results implicate ERV enhancer co-option as a mechanism underlying the extensive evolutionary diversification of placental development.
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA. echuong@stanford.edu
authors: Edward B
authors: EB
authors: Chuong
authors: M A Karim
authors: MA
authors: Rumi
authors: Michael J
authors: MJ
authors: Soares
authors: Julie C
authors: JC
authors: Baker
mesh_terms: D000107:Acetylation; D000818:Animals; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D016678:Genome; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D010920:Placenta / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D006657:Histones; D011495:Histone-Lysine N-Methyltransferase
references: Genome Biol. 2011 Aug 22;12(8):R83
references: 21859476
references: Genome Biol. 2009;10(3):R25
references: 19261174
references: Nat Rev Genet. 2001 Jul;2(7):538-48
references: 11433360
references: Nat Rev Genet. 2008 May;9(5):397-405
references: 18368054
references: PLoS Comput Biol. 2007 Jul;3(7):e137
references: 17630829
references: Genes Dev. 2011 Aug 1;25(15):1654-61
references: 21828274
references: Cytogenet Genome Res. 2005;110(1-4):353-64
references: 16093687
references: Dev Biol. 2004 Nov 1;275(1):158-69
references: 15464579
references: Biol Reprod. 2011 Mar;84(3):412-21
references: 21106963
references: Bioinformatics. 2009 Jul 15;25(14):1754-60
references: 19451168
references: Virology. 2011 Mar 15;411(2):273-87
references: 21251689
references: Placenta. 2009 Mar;30 Suppl A:S15-8
references: 19007983
references: Genome Res. 2008 May;18(5):695-705
references: 18340042
references: Genome Res. 2008 Nov;18(11):1752-62
references: 18682548
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D77-82
references: 18842628
references: Nature. 2000 Mar 2;404(6773):95-9
references: 10716450
references: Cell. 2005 Dec 2;123(5):917-29
references: 16325584
references: PLoS One. 2010 Jan 19;5(1):e8768
references: 20098735
references: Nat Rev Genet. 2009 Oct;10(10):691-703
references: 19763152
references: Endocrinology. 1991 Dec;129(6):2895-906
references: 1954876
references: Genome Biol. 2010;11(10):R106
references: 20979621
references: Nat Rev Genet. 2012 Mar 16;13(4):283-96
references: 22421730
references: Nat Genet. 2010 Apr;42(4):343-7
references: 20208536
references: Nature. 2012 Aug 2;488(7409):116-20
references: 22763441
references: Genome Biol. 2008;9(9):R137
references: 18798982
references: Dev Biol. 2011 Mar 1;351(1):110-9
references: 21215265
references: Am Nat. 2004 May;163(5):635-53
references: 15122484
references: Nat Genet. 2011 Sep 25;43(11):1154-9
references: 21946353
references: Genomics. 2009 Jan;93(1):33-41
references: 18848617
references: Nat Biotechnol. 2010 May;28(5):495-501
references: 20436461
references: Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10783-90
references: 20479220
references: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3319-23
references: 10725351
references: Q Rev Biol. 1993 Dec;68(4):495-532
references: 8115596
references: Mol Biol Evol. 2010 Jun;27(6):1221-5
references: 20123797
references: Cell. 2011 Sep 16;146(6):1029-41
references: 21925323
references: Nature. 2004 Apr 1;428(6982):493-521
references: 15057822
references: Bioinformatics. 2010 Mar 15;26(6):841-2
references: 20110278
references: Nat Rev Genet. 2011 Jan;12(1):7-18
references: 21116306
references: Nat Cell Biol. 2008 Nov;10(11):1280-90
references: 18836439
references: Curr Biol. 2012 Aug 7;22(15):R609-13
references: 22877784
references: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W202-8
references: 19458158
references: Cell. 2008 Jul 11;134(1):25-36
references: 18614008
references: Nature. 2002 Dec 5;420(6915):520-62
references: 12466850