title: Methylome, transcriptome, and PPAR(γ) cistrome analyses reveal two epigenetic transitions in fat cells.
abstract: Although DNA modification is adaptive to extrinsic demands, little is known about epigenetic alterations associated with adipose differentiation and reprogramming. We systematically characterized the global trends of our methylome and transcriptome data with reported PPAR(γ) cistrome data. Our analysis revealed that DNA methylation was altered between induced pluripotent stem cells (iPSCs) and adipose derived stem cells (ADSCs). Surprisingly, DNA methylation was not obviously changed in differentiation from ADSCs to mature fat cells (FatCs). This indicates that epigenetic predetermination of the adipogenic fate is almost established prior to substantial expression of the lineage. Furthermore, the majority of the PPAR(γ) cistrome corresponded to the pre-set methylation profile between ADSCs and FatCs. In contrast to the pre-set model, we found that a subset of PPAR(γ)-binding sites for late-expressing genes such as Adiponectin and Adiponectin receptor2 were differentially methylated independently of the early program. Thus, these analyses identify two types of epigenetic mechanisms that distinguish the pre-set cell fate and later stages of adipose differentiation.
authors.affiliation: Research Center for Stem Cell Engineering; National Institute of Advanced Industrial Science and Technology (AIST); Tsukuba, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takada
authors.affiliation: Computational Biology Research Center; National Institute of Advanced Industrial Science and Technology (AIST); Tokyo, Japan; Japan Science and Technology Agency; Kawaguchi, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Computational Biology Research Center; National Institute of Advanced Industrial Science and Technology (AIST); Tokyo, Japan; Japan Science and Technology Agency; Kawaguchi, Japan.
authors.forename: Toutai
authors.initials: T
authors.lastname: Mituyama
authors.affiliation: Gene Expression Laboratory; Salk Institute for Biological Studies; La Jolla, CA USA.
authors.forename: Zong
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Gene Expression Laboratory; Salk Institute for Biological Studies; La Jolla, CA USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yoshihara
authors.affiliation: Gene Expression Laboratory; Salk Institute for Biological Studies; La Jolla, CA USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jacinto
authors.affiliation: Gene Expression Laboratory; Salk Institute for Biological Studies; La Jolla, CA USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Downes
authors.affiliation: Gene Expression Laboratory; Salk Institute for Biological Studies; La Jolla, CA USA; Howard Hughes Medical Institute; Salk Institute for Biological Studies; La Jolla, CA USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.affiliation: Research Center for Stem Cell Engineering; National Institute of Advanced Industrial Science and Technology (AIST); Tsukuba, Japan.
authors.forename: Yasuyuki S
authors.initials: YS
authors.lastname: Kida
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C475420:ADIPOR2 protein, human; D052242:Adiponectin; D047495:PPAR gamma; D054419:Receptors, Adiponectin
keywords: DNA methylation; adipose derived stem cells; epigenetics; fat cells; fat differentiation; induced pluripotent stem cells; reprogramming
references.citation: Cell. 2010 Oct 1;143(1):156-69
references.pmid: 20887899
references.citation: J Biol Chem. 2010 Sep 24;285(39):30034-41
references.pmid: 20656681
references.citation: PLoS One. 2012;7(12):e51302
references.pmid: 23251491
references.citation: Nat Protoc. 2012 Sep;7(9):1728-40
references.pmid: 22936215
references.citation: PLoS Genet. 2011 May;7(5):e1002085
references.pmid: 21637780
references.citation: Trends Endocrinol Metab. 2012 Feb;23(2):56-64
references.pmid: 22079269
references.citation: Genome Biol. 2011 Jul 06;12(7):R62
references.pmid: 21733148
references.citation: Diabetes. 2007 Jun;56(6):1517-26
references.pmid: 17389330
references.citation: Mol Cell. 2012 Aug 24;47(4):633-47
references.pmid: 22841485
references.citation: Nature. 2011 Mar 3;471(7336):68-73
references.pmid: 21289626
references.citation: Regen Med. 2010 Jul;5(4):531-44
references.pmid: 20632857
references.citation: Mediators Inflamm. 2010;2010:802078
references.pmid: 20671929
references.citation: Genes Dev. 2002 Jan 1;16(1):6-21
references.pmid: 11782440
references.citation: Diabetes. 2006 Jun;55(6):1537-45
references.pmid: 16731815
references.citation: Genome Biol. 2009;10(3):R25
references.pmid: 19261174
references.citation: Nat Biotechnol. 2010 May;28(5):511-5
references.pmid: 20436464
references.citation: PLoS Genet. 2009 Aug;5(8):e1000602
references.pmid: 19680444
references.citation: Genome Res. 2012 Aug;22(8):1407-18
references.pmid: 22684279
references.citation: BMC Bioinformatics. 2009 Feb 03;10:48
references.pmid: 19192299
references.citation: Nat Protoc. 2011 Mar;6(3):346-58
references.pmid: 21372815
references.citation: Curr Opin Genet Dev. 1993 Apr;3(2):226-31
references.pmid: 8504247
references.citation: Trends Endocrinol Metab. 2009 Apr;20(3):107-14
references.pmid: 19269847
references.citation: Nucleic Acids Res. 2014 Apr;42(6):e45
references.pmid: 24423865
references.citation: EMBO J. 2011 Apr 20;30(8):1459-72
references.pmid: 21427703
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15720-5
references.pmid: 19805220
references.citation: Nature. 2009 Nov 19;462(7271):315-22
references.pmid: 19829295
references.citation: Adipocyte. 2012 Jan 1;1(1):13-24
references.pmid: 23700507
references.citation: J Biol Chem. 2011 Aug 5;286(31):27836-47
references.pmid: 21680747
references.citation: Genes Dev. 2013 Jun 15;27(12):1318-38
references.pmid: 23788621
references.citation: Bioinformatics. 2009 May 1;25(9):1105-11
references.pmid: 19289445
references.citation: Diabetes. 1998 Apr;47(4):507-14
references.pmid: 9568680
references.citation: Nat Biotechnol. 2011 Jan;29(1):24-6
references.pmid: 21221095
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3558-63
references.pmid: 20133714
references.citation: Diabetes. 2003 Jul;52(7):1655-63
references.pmid: 12829629
references.citation: Nat Genet. 2002 Jun;31(2):175-9
references.pmid: 12021783
references.citation: Epigenetics. 2011 Jun;6(6):692-702
references.pmid: 21593595
references.citation: J Biol Chem. 1996 May 3;271(18):10697-703
references.pmid: 8631877
references.citation: Nat Med. 2013 May;19(5):557-66
references.pmid: 23652116