<i>Drosophila</i> insulator proteins exhibit in vivo liquid-liquid phase separation properties.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
19 07 2022
19 07 2022
Historique:
received:
27
05
2022
revised:
05
07
2022
accepted:
06
07
2022
entrez:
19
7
2022
pubmed:
20
7
2022
medline:
22
7
2022
Statut:
epublish
Résumé
Mounting evidence implicates liquid-liquid phase separation (LLPS), the condensation of biomolecules into liquid-like droplets in the formation and dissolution of membraneless intracellular organelles (MLOs). Cells use MLOs or condensates for various biological processes, including emergency signaling and spatiotemporal control over steady-state biochemical reactions and heterochromatin formation. Insulator proteins are architectural elements involved in establishing independent domains of transcriptional activity within eukaryotic genomes. In <i>Drosophila</i>, insulator proteins form nuclear foci known as insulator bodies in response to osmotic stress. However, the mechanism through which insulator proteins assemble into bodies is yet to be investigated. Here, we identify signatures of LLPS by insulator bodies, including high disorder tendency in insulator proteins, scaffold-client-dependent assembly, extensive fusion behavior, sphericity, and sensitivity to 1,6-hexanediol. We also show that the cohesin subunit Rad21 is a component of insulator bodies, adding to the known insulator protein constituents and γH2Av. Our data suggest a concerted role of cohesin and insulator proteins in insulator body formation and under physiological conditions. We propose a mechanism whereby these architectural proteins modulate 3D genome organization through LLPS.
Identifiants
pubmed: 35853678
pii: 5/12/e202201536
doi: 10.26508/lsa.202201536
pmc: PMC9297610
pii:
doi:
Substances chimiques
Drosophila Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : P40 OD010949
Pays : United States
Informations de copyright
© 2022 Amankwaa et al.
Références
Cell. 2015 Nov 5;163(4):934-46
pubmed: 26544940
Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):E3605-11
pubmed: 24003126
Trends Genet. 2019 Jul;35(7):542-551
pubmed: 31130395
Genome Biol. 2021 Aug 17;22(1):229
pubmed: 34404448
Mol Cell Biol. 1992 Mar;12(3):928-35
pubmed: 1545824
Biophys J. 2017 Jan 10;112(1):16-21
pubmed: 28076807
Genes (Basel). 2019 Dec 17;10(12):
pubmed: 31861077
Nature. 2019 Aug;572(7770):543-548
pubmed: 31391587
Genome Res. 2016 Jan;26(1):70-84
pubmed: 26518482
Nat Commun. 2021 Jul 7;12(1):4170
pubmed: 34234130
Mol Cell. 2015 Mar 5;57(5):936-947
pubmed: 25747659
Cell. 2002 Oct 18;111(2):151-4
pubmed: 12408858
Nucleic Acids Res. 2018 Jul 2;46(W1):W329-W337
pubmed: 29860432
Dev Biol. 2011 Aug 15;356(2):398-410
pubmed: 21651900
Nucleic Acids Res. 2020 Jan 8;48(D1):D354-D359
pubmed: 31584089
Science. 2018 Feb 9;359(6376):698-701
pubmed: 29439243
Genome Biol. 2020 Jan 7;21(1):5
pubmed: 31910870
Trends Cell Biol. 2020 Jan;30(1):4-14
pubmed: 31753533
Biophys Rev. 2020 Apr;12(2):519-539
pubmed: 32189162
Nature. 2017 Jul 13;547(7662):241-245
pubmed: 28636597
Adv Genet. 1996;34:1-497
pubmed: 9348397
Nucleic Acids Res. 2012 Jul;40(12):5415-31
pubmed: 22406832
J Biol Chem. 2020 Feb 21;295(8):2375-2384
pubmed: 31911439
Genes (Basel). 2019 Sep 28;10(10):
pubmed: 31569427
Elife. 2018 Feb 09;7:
pubmed: 29424691
Science. 2018 Jul 27;361(6400):
pubmed: 29930091
Cell. 2014 Dec 18;159(7):1665-80
pubmed: 25497547
Arch Biochem Biophys. 2008 Jan 1;469(1):132-41
pubmed: 17931593
Genome Res. 2019 Aug;29(8):1235-1249
pubmed: 31201210
Biol Open. 2016 Sep 15;5(9):1266-74
pubmed: 27464669
Dev Cell. 2008 Feb;14(2):239-51
pubmed: 18267092
J Cell Biol. 2007 Nov 5;179(3):437-49
pubmed: 17984320
Life Sci Alliance. 2021 Feb 3;4(4):
pubmed: 33536240
Biochemistry. 2018 May 1;57(17):2424-2431
pubmed: 29381060
Cell. 2018 Jul 26;174(3):744-757.e24
pubmed: 29887377
EMBO Rep. 2008 Oct;9(10):1019-26
pubmed: 18758438
Mol Cell. 2018 May 17;70(4):730-744.e6
pubmed: 29706538
Nat Rev Mol Cell Biol. 2017 May;18(5):285-298
pubmed: 28225081
Nucleic Acids Res. 2021 Oct 11;49(18):10524-10541
pubmed: 33836078
Elife. 2019 May 07;8:
pubmed: 31038454
Nature. 2019 Jun;570(7761):395-399
pubmed: 31168090
Genetics. 2017 Jan;205(1):5-24
pubmed: 28049701
Nucleic Acids Res. 2009 Jan;37(Database issue):D181-4
pubmed: 18984612
Dev Cell. 2010 Dec 14;19(6):819-30
pubmed: 21145498
Curr Opin Struct Biol. 2019 Oct;58:88-96
pubmed: 31252218
Elife. 2016 Sep 07;5:
pubmed: 27602576
Genetics. 2000 May;155(1):141-57
pubmed: 10790390
EMBO J. 2001 May 15;20(10):2518-27
pubmed: 11350941
Elife. 2020 Apr 06;9:
pubmed: 32250245
BMC Bioinformatics. 2022 Feb 15;23(1):72
pubmed: 35168563
Cell. 2015 May 21;161(5):1012-1025
pubmed: 25959774
EMBO J. 2017 Dec 15;36(24):3600-3618
pubmed: 29217590
Annu Rev Genet. 2009;43:525-58
pubmed: 19886810
Sci Adv. 2021 Feb 10;7(7):
pubmed: 33568486
Science. 2020 Feb 7;367(6478):694-699
pubmed: 32029630
Nature. 2018 Jul;559(7713):211-216
pubmed: 29973724
Mol Cell. 2005 Oct 7;20(1):105-16
pubmed: 16209949
Nat Commun. 2020 Dec 2;11(1):6178
pubmed: 33268790
EMBO J. 2017 Dec 15;36(24):3573-3599
pubmed: 29217591
PLoS Genet. 2013;9(7):e1003606
pubmed: 23861668
Gene. 2022 Apr 20;819:146208
pubmed: 35092858
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
J Cell Sci. 2004 Aug 1;117(Pt 17):3935-45
pubmed: 15265990
Cell. 2018 Jan 25;172(3):590-604.e13
pubmed: 29373831
Nat Commun. 2021 Feb 17;12(1):1085
pubmed: 33597515
Science. 2009 Jun 26;324(5935):1729-32
pubmed: 19460965
Biophys J. 2004 Jun;86(6):3993-4003
pubmed: 15189895
Pac Symp Biocomput. 2020;25:207-218
pubmed: 31797598
Biochemistry. 2018 May 1;57(17):2540-2548
pubmed: 29644850
Genes (Basel). 2019 Dec 10;10(12):
pubmed: 31835574
Bioessays. 2019 Sep;41(9):e1900048
pubmed: 31264253
Cell. 1998 Feb 20;92(4):511-21
pubmed: 9491892
Science. 2017 Sep 22;357(6357):
pubmed: 28935776
Genome Biol. 2014 Jun 30;15(6):R82
pubmed: 24981874
Mol Cell. 2007 Apr 13;26(1):103-15
pubmed: 17434130
Cell. 2017 May 18;169(5):930-944.e22
pubmed: 28525758
PLoS Genet. 2020 Dec 7;16(12):e1009229
pubmed: 33284803
Science. 2008 Nov 28;322(5906):1365-8
pubmed: 19039133
Chromosome Res. 2003;11(5):485-502
pubmed: 12971724
Cell. 2019 Jan 24;176(3):419-434
pubmed: 30682370
Mol Cell. 2016 Jul 7;63(1):72-85
pubmed: 27392146
Mol Cell. 2000 Nov;6(5):1025-35
pubmed: 11106742
Curr Opin Genet Dev. 2020 Apr;61:1-8
pubmed: 32199341
Curr Opin Plant Biol. 2019 Apr;48:36-46
pubmed: 31035031
Chromosoma. 2010 Apr;119(2):177-94
pubmed: 20033198
Cell Rep. 2019 Mar 12;26(11):2890-2903.e3
pubmed: 30865881
Annu Rev Cell Dev Biol. 2014;30:39-58
pubmed: 25288112
Science. 2018 Jul 27;361(6400):
pubmed: 29930090
Cell. 2018 Jul 26;174(3):688-699.e16
pubmed: 29961577
Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6697-E6706
pubmed: 29967174
Elife. 2020 Nov 10;9:
pubmed: 33170773
Trends Cell Biol. 2018 Jun;28(6):420-435
pubmed: 29602697
Trends Cell Biol. 2021 Aug;31(8):671-685
pubmed: 33771451
Nat Genet. 2020 Nov;52(11):1151-1157
pubmed: 33077913
Nucleus. 2020 Dec;11(1):132-148
pubmed: 32631111
Am J Physiol Cell Physiol. 2011 Apr;300(4):C723-42
pubmed: 21209361
BMC Cell Biol. 2010 Dec 31;11:101
pubmed: 21194420
Int J Mol Sci. 2020 Aug 27;21(17):
pubmed: 32867340
Genes Dev. 2019 Dec 1;33(23-24):1619-1634
pubmed: 31594803
Nat Commun. 2018 Jan 15;9(1):188
pubmed: 29335463
Biophys J. 2020 Feb 4;118(3):753-764
pubmed: 31952807
BMC Bioinformatics. 2006 Apr 17;7:208
pubmed: 16618368
Genomics Proteomics Bioinformatics. 2021 Feb;19(1):13-24
pubmed: 33610793
Brief Funct Genomics. 2020 Mar 23;19(2):111-118
pubmed: 31971237
Mol Cell. 2019 Nov 7;76(3):395-411.e13
pubmed: 31522987
Trends Biochem Sci. 1990 Mar;15(3):98-102
pubmed: 2158158
Genome Biol. 2009;10(5):R50
pubmed: 19432952
Nat Commun. 2018 Feb 26;9(1):842
pubmed: 29483575
Nat Chem Biol. 2020 Mar;16(3):257-266
pubmed: 31792445
J Biol Chem. 2021 Oct;297(4):101194
pubmed: 34537246
Curr Opin Struct Biol. 2015 Jun;32:102-12
pubmed: 25863585
Mar Drugs. 2014 Aug 21;12(8):4616-34
pubmed: 25196936
Toxicon. 2019 Mar 15;160:1-7
pubmed: 30639658
Genes Dev. 2019 Jul 1;33(13-14):799-813
pubmed: 31171700
Biophys J. 2021 Apr 6;120(7):1187-1197
pubmed: 33582133
Trends Cell Biol. 2005 Feb;15(2):84-91
pubmed: 15695095
J Cell Biol. 2013 Jul 22;202(2):261-76
pubmed: 23878275
EMBO J. 2012 Jan 18;31(2):330-50
pubmed: 22085927
Nat Commun. 2020 Nov 6;11(1):5642
pubmed: 33159068
J Cell Biol. 2003 Aug 18;162(4):565-74
pubmed: 12925706
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4334-9
pubmed: 21368180
Int J Mol Sci. 2019 Nov 05;20(21):
pubmed: 31694155
Mol Cell. 2017 Sep 7;67(5):837-852.e7
pubmed: 28826674
J Mol Biol. 2018 Nov 2;430(23):4666-4684
pubmed: 30099028
Mol Cell. 2004 Dec 3;16(5):737-48
pubmed: 15574329
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13392-7
pubmed: 23901099
Chem Rev. 2014 Jul 9;114(13):6589-631
pubmed: 24773235
Mol Cell. 2010 Jul 9;39(1):8-24
pubmed: 20603072
Biochem J. 1988 Nov 15;256(1):283-90
pubmed: 2851982
Polymers (Basel). 2019 Jun 04;11(6):
pubmed: 31167414
J Biol Chem. 2019 May 3;294(18):7137-7150
pubmed: 30587571
Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):11964-11969
pubmed: 30301810
Nature. 1995 Aug 3;376(6539):424-7
pubmed: 7630417
G3 (Bethesda). 2013 Sep 04;3(9):1539-43
pubmed: 23833215
PLoS Comput Biol. 2012;8(10):e1002709
pubmed: 23055912
Elife. 2019 Mar 20;8:
pubmed: 30893049
EMBO Rep. 2008 May;9(5):440-5
pubmed: 18369369
Elife. 2015 Aug 04;4:e06807
pubmed: 26238190
Nat Struct Mol Biol. 2018 Sep;25(9):833-840
pubmed: 30127355
Database (Oxford). 2018 Jan 1;2018:
pubmed: 30576490
Cell Mol Life Sci. 2014 Nov;71(21):4089-113
pubmed: 25012699