Detailed Functional Characterization of a Waist-Hip Ratio Locus in 7p15.2 Defines an Enhancer Controlling Adipocyte Differentiation.
Genetics
Human Genetics
Specialized Functions of Cells
Transcriptomics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
25 Oct 2019
25 Oct 2019
Historique:
received:
18
02
2019
revised:
10
07
2019
accepted:
05
09
2019
pubmed:
27
9
2019
medline:
27
9
2019
entrez:
27
9
2019
Statut:
ppublish
Résumé
We combined CAGE sequencing in human adipocytes during differentiation with data from genome-wide association studies to identify an enhancer in the SNX10 locus on chromosome 7, presumably involved in body fat distribution. Using reporter assays and CRISPR-Cas9 gene editing in human cell lines, we characterized the role of the enhancer in adipogenesis. The enhancer was active during adipogenesis and responded strongly to insulin and isoprenaline. The allele associated with increased waist-hip ratio in human genetic studies was associated with higher enhancer activity. Mutations of the enhancer resulted in less adipocyte differentiation. RNA sequencing of cells with disrupted enhancer showed reduced expression of established adipocyte markers, such as ADIPOQ and LPL, and identified CHI3L1 on chromosome 1 as a potential gene involved in adipocyte differentiation. In conclusion, we identified and characterized an enhancer in the SNX10 locus and outlined its plausible mechanisms of action and downstream targets.
Identifiants
pubmed: 31557715
pii: S2589-0042(19)30343-8
doi: 10.1016/j.isci.2019.09.006
pmc: PMC6817687
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
42-59Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Références
J Biol Chem. 2003 Jan 24;278(4):2581-4
pubmed: 12426306
Nat Biotechnol. 2003 May;21(5):553-8
pubmed: 12679786
Nat Genet. 2018 Jan;50(1):26-41
pubmed: 29273807
Nature. 2000 May 25;405(6785):482-5
pubmed: 10839546
Mol Cell Biol. 2013 Oct;33(19):3864-78
pubmed: 23897429
Genomics. 2016 Jun;107(6):248-54
pubmed: 27126307
Nat Genet. 1994 Jul;7(3):433-9
pubmed: 7920665
Nat Commun. 2017 Apr 26;8:14977
pubmed: 28443625
Oncol Rep. 2018 Nov;40(5):2916-2925
pubmed: 30226601
Nat Commun. 2016 Feb 01;7:10495
pubmed: 26833246
Hum Mol Genet. 2004 Aug 1;13(15):1587-97
pubmed: 15175273
PLoS Genet. 2017 Apr 27;13(4):e1006528
pubmed: 28448500
Hepatology. 2010 Mar;51(3):881-90
pubmed: 20146264
Sci Rep. 2015 May 22;5:9930
pubmed: 26001136
Am J Hum Genet. 2017 Jul 6;101(1):5-22
pubmed: 28686856
Nature. 2015 Feb 12;518(7538):187-196
pubmed: 25673412
Science. 2015 Feb 27;347(6225):1010-4
pubmed: 25678556
Nat Genet. 2010 Nov;42(11):949-60
pubmed: 20935629
Science. 2000 Aug 11;289(5481):950-3
pubmed: 10937998
Mol Cell Endocrinol. 2001 Feb 14;172(1-2):223-33
pubmed: 11165056
Cell Mol Life Sci. 2010 Apr;67(8):1277-92
pubmed: 20107860
Lancet. 2012 Dec 15;380(9859):2095-128
pubmed: 23245604
Stem Cells Dev. 2011 Feb;20(2):259-67
pubmed: 20486779
Nat Genet. 2010 Nov;42(11):937-48
pubmed: 20935630
Nat Genet. 2004 Apr;36(4):371-6
pubmed: 14991056
Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13127-32
pubmed: 25157153
FEBS J. 2017 Jun;284(11):1738-1747
pubmed: 28391634
Int J Oncol. 2014 Jun;44(6):1915-22
pubmed: 24714841
N Engl J Med. 2008 Apr 17;358(16):1682-91
pubmed: 18403759
Nat Rev Mol Cell Biol. 2008 Mar;9(3):219-30
pubmed: 18270516
Nature. 1991 May 9;351(6322):153-5
pubmed: 1709450
Biochem Biophys Res Commun. 2009 Oct 23;388(3):511-6
pubmed: 19666003
Am J Hum Genet. 2002 Mar;70(3):604-11
pubmed: 11813134
Mol Cell Biol. 2000 Jan;20(2):429-40
pubmed: 10611221
PLoS Genet. 2015 Oct 01;11(10):e1005378
pubmed: 26426971
Cell. 1996 May 3;85(3):403-14
pubmed: 8616895
Bioinformatics. 2002 Feb;18(2):333-4
pubmed: 11847087
Sci STKE. 2000 Oct 03;2000(52):pe1
pubmed: 11752612
Cell. 1990 Sep 21;62(6):1205-15
pubmed: 2169352
J Med Genet. 2009 Mar;46(3):192-7
pubmed: 19066168
Nat Genet. 2012 Dec;44(12):1355-9
pubmed: 23104006
Genes Dev. 2014 May 1;28(9):1018-28
pubmed: 24788520
Diabetes. 2017 Jan;66(1):218-230
pubmed: 27803022
J Mol Cell Biol. 2013 Feb;5(1):3-13
pubmed: 22935141
J Mol Endocrinol. 2007 Oct;39(4):261-77
pubmed: 17909266
Am J Respir Crit Care Med. 2015 Apr 1;191(7):746-57
pubmed: 25629580
Mol Immunol. 2018 Jan;93:107-114
pubmed: 29172088
J Immunol. 2010 Jun 15;184(12):6773-81
pubmed: 20483747
Nat Commun. 2017 May 24;8:15539
pubmed: 28537267
J Biol Chem. 2004 Dec 10;279(50):52361-5
pubmed: 15504739
Nat Genet. 2013 Jun;45(6):690-6
pubmed: 23583978
Nutr Metab (Lond). 2011 May 12;8(1):30
pubmed: 21569430
Histochemistry. 1992 Jul;97(6):493-7
pubmed: 1385366
Diabetologia. 2006 Apr;49(4):678-84
pubmed: 16477437
Clin Chem. 2010 Jul;56(7):1107-18
pubmed: 20431052
Diabetes. 2009 May;58(5):1050-7
pubmed: 19188425
EMBO Mol Med. 2013 Oct;5(10):1602-12
pubmed: 24009212
PLoS Genet. 2016 Jun 29;12(6):e1006166
pubmed: 27355579
Nat Commun. 2016 Jan 21;7:10023
pubmed: 26831199
Metabolism. 2012 Apr;61(4):562-8
pubmed: 22036069
Hum Mol Genet. 1997 Oct;6(11):1873-8
pubmed: 9302265
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3324-9
pubmed: 15728361
Mol Cell Biol. 2007 Jan;27(2):743-57
pubmed: 17060461
Cell. 1989 Nov 3;59(3):405-8
pubmed: 2572326
Sci Rep. 2016 Jun 28;6:28897
pubmed: 27349231
Hum Mol Genet. 2019 Jan 1;28(1):166-174
pubmed: 30239722
J Mol Biol. 2007 Apr 13;367(5):1270-80
pubmed: 17320102
Nature. 2015 Feb 12;518(7538):197-206
pubmed: 25673413
Biochem J. 2004 Jun 15;380(Pt 3):651-9
pubmed: 15015934
Am J Hum Genet. 2007 Jan;80(1):12-8
pubmed: 17160890
Am J Hum Genet. 2006 Apr;78(4):604-14
pubmed: 16532391