A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis.
ATAC-seq
CUT&RUN
Chromatin
DNA binding
Gene regulation
HIF1α
Hypoxia
RNA-seq
Transcriptional regulation
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
03 Jul 2021
03 Jul 2021
Historique:
received:
16
02
2021
accepted:
09
06
2021
entrez:
3
7
2021
pubmed:
4
7
2021
medline:
7
7
2021
Statut:
epublish
Résumé
During eye lens development the embryonic vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia and the master regulator of the hypoxic response, hypoxia-inducible transcription factor 1 (HIF1), in the regulation of genes required for lens fiber cell differentiation, structure and transparency. Here, we employed a multiomics approach combining CUT&RUN, RNA-seq and ATACseq analysis to establish the genomic complement of lens HIF1α binding sites, genes activated or repressed by HIF1α and the chromatin states of HIF1α-regulated genes. CUT&RUN analysis revealed 8375 HIF1α-DNA binding complexes in the chick lens genome. One thousand one hundred ninety HIF1α-DNA binding complexes were significantly clustered within chromatin accessible regions (χ These data establish the first functional map of genomic HIF1α-DNA complexes in the eye lens. They identify HIF1α as an important regulator of a wide-variety of genes previously shown to be critical for lens formation and function and they reveal a requirement for HIF1α in the regulation of a wide-variety of genes not yet examined for lens function. They support a requirement for HIF1α in lens fiber cell formation, structure and function and they provide a basis for understanding the potential roles and requirements for HIF1α in the development, structure and function of more complex tissues.
Sections du résumé
BACKGROUND
BACKGROUND
During eye lens development the embryonic vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia and the master regulator of the hypoxic response, hypoxia-inducible transcription factor 1 (HIF1), in the regulation of genes required for lens fiber cell differentiation, structure and transparency. Here, we employed a multiomics approach combining CUT&RUN, RNA-seq and ATACseq analysis to establish the genomic complement of lens HIF1α binding sites, genes activated or repressed by HIF1α and the chromatin states of HIF1α-regulated genes.
RESULTS
RESULTS
CUT&RUN analysis revealed 8375 HIF1α-DNA binding complexes in the chick lens genome. One thousand one hundred ninety HIF1α-DNA binding complexes were significantly clustered within chromatin accessible regions (χ
CONCLUSIONS
CONCLUSIONS
These data establish the first functional map of genomic HIF1α-DNA complexes in the eye lens. They identify HIF1α as an important regulator of a wide-variety of genes previously shown to be critical for lens formation and function and they reveal a requirement for HIF1α in the regulation of a wide-variety of genes not yet examined for lens function. They support a requirement for HIF1α in lens fiber cell formation, structure and function and they provide a basis for understanding the potential roles and requirements for HIF1α in the development, structure and function of more complex tissues.
Identifiants
pubmed: 34215186
doi: 10.1186/s12864-021-07795-9
pii: 10.1186/s12864-021-07795-9
pmc: PMC8254356
doi:
Substances chimiques
Chromatin
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
497Subventions
Organisme : NEI NIH HHS
ID : R01 EY029708
Pays : United States
Références
Autophagy. 2019 Sep;15(9):1606-1619
pubmed: 30859901
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W202-8
pubmed: 19458158
J Cell Biol. 1988 Dec;107(6 Pt 2):2729-36
pubmed: 2462567
Nat Protoc. 2018 May;13(5):1006-1019
pubmed: 29651053
Exp Eye Res. 2004 Dec;79(6):859-68
pubmed: 15642323
Dev Biol. 2008 Sep 1;321(1):111-22
pubmed: 18588871
Biochem Biophys Res Commun. 2019 May 14;512(4):927-933
pubmed: 30929925
Autophagy. 2008 Apr;4(3):354-6
pubmed: 18623629
Invest Ophthalmol Vis Sci. 2017 May 1;58(5):2666-2684
pubmed: 28525556
Open Biol. 2019 Dec;9(12):190220
pubmed: 31847788
Biomaterials. 2018 May;165:48-55
pubmed: 29501969
Dev Biol. 2019 Sep 1;453(1):86-104
pubmed: 31136738
Pflugers Arch. 2005 Sep;450(6):363-71
pubmed: 16007431
Invest Ophthalmol Vis Sci. 2013 Mar 01;54(3):1582-90
pubmed: 23385791
Biochim Biophys Acta Mol Basis Dis. 2017 Jan;1863(1):21-32
pubmed: 27702626
J Clin Invest. 2007 Dec;117(12):3810-20
pubmed: 18037992
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6794-9
pubmed: 17420462
J Physiol. 2004 Sep 15;559(Pt 3):883-98
pubmed: 15272034
Med Sci Monit. 2018 Oct 17;24:7424-7430
pubmed: 30332398
Nat Med. 2003 Jun;9(6):677-84
pubmed: 12778166
Dev Dyn. 2002 Aug;224(4):361-72
pubmed: 12203728
J Cell Sci. 2018 Nov 20;131(22):
pubmed: 30404825
Mol Cell Biol. 2007 Oct;27(20):7236-47
pubmed: 17709399
Elife. 2017 Jan 16;6:
pubmed: 28079019
Free Radic Biol Med. 2001 Sep 1;31(5):651-8
pubmed: 11522450
Philos Trans R Soc Lond B Biol Sci. 2011 Apr 27;366(1568):1250-64
pubmed: 21402584
Cancer Res. 2001 Sep 15;61(18):6669-73
pubmed: 11559532
Exp Eye Res. 2009 Feb;88(2):270-6
pubmed: 18782574
Cells. 2019 Mar 03;8(3):
pubmed: 30832409
Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4490-9
pubmed: 17003444
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
Mol Cell Biol. 2009 May;29(10):2570-81
pubmed: 19273585
Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5
pubmed: 27079975
Exp Eye Res. 2018 Sep;174:173-184
pubmed: 29879393
J Exp Biol. 2003 Dec;206(Pt 23):4353-61
pubmed: 14581604
Genes Dev. 1998 Dec 1;12(23):3764-75
pubmed: 9851982
Nat Protoc. 2012 Sep;7(9):1728-40
pubmed: 22936215
J Cell Sci. 2009 Apr 15;122(Pt 8):1055-7
pubmed: 19339544
J Cell Sci. 2000 Jun;113 ( Pt 11):1913-21
pubmed: 10806102
J Hepatol. 2018 Oct;69(4):886-895
pubmed: 29803899
Cell Prolif. 2017 Oct;50(5):
pubmed: 28752896
Dev Dyn. 2009 Sep;238(9):2280-91
pubmed: 19623612
Nature. 2007 Mar 22;446(7134):444-8
pubmed: 17334357
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
Curr Mol Med. 2010 Dec;10(9):864-75
pubmed: 21091420
Clin Exp Pharmacol Physiol. 2017 Mar;44(3):327-334
pubmed: 28004401
Database (Oxford). 2013 Oct 31;2013:bat074
pubmed: 24178989
Oncogene. 2008 Dec;27 Suppl 1:S114-27
pubmed: 19641497
Exp Eye Res. 2019 May;182:1-9
pubmed: 30849386
Exp Physiol. 2016 Jan;101(1):28-32
pubmed: 26391197
G3 (Bethesda). 2014 Jun 13;4(8):1515-27
pubmed: 24928582
Philos Trans R Soc Lond B Biol Sci. 2011 Apr 27;366(1568):1219-33
pubmed: 21402582
Biomedicines. 2018 Apr 22;6(2):
pubmed: 29690561
Bioinformatics. 2011 Jun 15;27(12):1653-9
pubmed: 21543442
Development. 2004 Apr;131(8):1813-24
pubmed: 15084465
Sci Rep. 2017 Jun 16;7(1):3644
pubmed: 28623342
Biochem J. 2008 Aug 15;414(1):19-29
pubmed: 18651837
Exp Eye Res. 2016 May;146:318-329
pubmed: 26992777
Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1171-7
pubmed: 20153717
Differentiation. 2018 Jul - Aug;102:40-52
pubmed: 30059908
Mol Biol Cell. 2017 Apr 1;28(7):907-921
pubmed: 28209733
Genome Biol. 2012 Sep 26;13(9):R50
pubmed: 22951020
PLoS One. 2012;7(12):e52948
pubmed: 23300831
Cell. 2018 Apr 5;173(2):430-442.e17
pubmed: 29606353
Mol Biol Cell. 2007 Mar;18(3):1018-29
pubmed: 17215516
Exp Eye Res. 2020 Sep;198:108129
pubmed: 32628953
Nat Biotechnol. 2015 Mar;33(3):290-5
pubmed: 25690850
EMBO J. 2004 May 5;23(9):1949-56
pubmed: 15071503
Curr Protoc Mol Biol. 2015 Jan 05;109:21.29.1-21.29.9
pubmed: 25559105
Curr Protoc. 2021 Mar;1(3):e90
pubmed: 33780170
Protein Sci. 2017 Jul;26(7):1266-1277
pubmed: 28329910
Cell Death Differ. 2017 Aug;24(8):1431-1442
pubmed: 28622289
Prog Retin Eye Res. 2018 Jan;62:58-76
pubmed: 29081352
FASEB J. 2016 Mar;30(3):1087-95
pubmed: 26590164
Blood. 2008 Jun 15;111(12):5571-80
pubmed: 18309031
FASEB J. 2009 Jan;23(1):204-13
pubmed: 18779379
J Membr Biol. 2012 Jul;245(7):357-68
pubmed: 22797938
Hugo J. 2010 Dec;4(1-4):35-48
pubmed: 22132063
Genome Res. 2006 Jan;16(1):1-10
pubmed: 16344566
Nat Rev Mol Cell Biol. 2015 Mar;16(3):178-89
pubmed: 25650798
Trends Genet. 2000 Sep;16(9):418-20
pubmed: 10973072
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Biochim Biophys Acta. 1978 Aug 3;542(1):28-38
pubmed: 208649
Dev Biol. 2005 Apr 1;280(1):1-14
pubmed: 15766743
Development. 2017 Jan 15;144(2):321-333
pubmed: 27993984
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Gene. 1991 Jul 22;103(2):193-200
pubmed: 1889745
Genome Biol. 2008;9(9):R137
pubmed: 18798982
J Clin Pathol. 2004 Oct;57(10):1009-14
pubmed: 15452150
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Bioinformatics. 2015 Jul 15;31(14):2382-3
pubmed: 25765347
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19500-5
pubmed: 18048346
BMC Ophthalmol. 2019 Nov 8;19(1):219
pubmed: 31703690
Genome Res. 2002 Jun;12(6):996-1006
pubmed: 12045153
Cell Death Dis. 2017 Oct 5;8(10):e3082
pubmed: 28981088
Mol Vis. 2010 Dec 15;16:2765-76
pubmed: 21197111
Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4961-70
pubmed: 18586877
EMBO Rep. 2010 Jan;11(1):45-51
pubmed: 20010802
Mol Biol Cell. 2010 Nov 1;21(21):3630-8
pubmed: 20844082
J Immunol. 2006 Aug 1;177(3):1941-55
pubmed: 16849508
Hum Genet. 2012 Feb;131(2):235-50
pubmed: 21769484
Nat Commun. 2018 Jan 17;9(1):251
pubmed: 29343683
J Clin Invest. 2009 Jan;119(1):203-12
pubmed: 19065046
FASEB J. 2003 Feb;17(2):315-7
pubmed: 12490536
Nucleic Acids Res. 2005 Sep 09;33(16):5190-8
pubmed: 16155188
Semin Cell Dev Biol. 2016 Apr;52:119-31
pubmed: 26868759
Prog Retin Eye Res. 2017 Sep;60:181-200
pubmed: 28411123
Int J Mol Sci. 2018 Oct 09;19(10):
pubmed: 30304871
Hum Mutat. 2019 Apr;40(4):380-391
pubmed: 30585370
Cancer Res. 2006 Apr 1;66(7):3688-98
pubmed: 16585195
Blood. 2011 Jun 9;117(23):e207-17
pubmed: 21447827
Differentiation. 2006 Jun;74(5):195-211
pubmed: 16759286
Prog Mol Biol Transl Sci. 2015;134:169-201
pubmed: 26310155
Nat Commun. 2019 Aug 7;10(1):3551
pubmed: 31391533
Exp Eye Res. 2002 Nov;75(5):485-90
pubmed: 12457861
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Elife. 2019 Jun 24;8:
pubmed: 31232687
Bioessays. 2014 Aug;36(8):798-806
pubmed: 24888900
Dev Biol. 2009 Aug 1;332(1):166-76
pubmed: 19481073
Exp Eye Res. 2018 Apr;169:28-37
pubmed: 29421327
Nat Rev Genet. 2009 Mar;10(3):161-72
pubmed: 19204718
Jpn J Ophthalmol. 2014 May;58(3):225-31
pubmed: 24687817
Autophagy. 2014 Jul;10(7):1193-211
pubmed: 24813396
Development. 2015 Jul 15;142(14):2405-12
pubmed: 26153230
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Trends Genet. 2017 Oct;33(10):677-702
pubmed: 28867048
Blood. 2003 Jul 15;102(2):712-7
pubmed: 12663450
PLoS One. 2008 Aug 27;3(8):e3078
pubmed: 18728783
Biol Open. 2019 Mar 26;8(3):
pubmed: 30890522
EMBO Rep. 2019 Jan;20(1):
pubmed: 30429208
Nature. 2008 Jul 10;454(7201):232-5
pubmed: 18454133
Autophagy. 2018;14(5):915-917
pubmed: 28614042
FASEB J. 2002 Aug;16(10):1151-62
pubmed: 12153983