Making Sense of the Tangle: Insights into Chromatin Folding and Gene Regulation.
Proximity ligation assays such as circularized chromosome conformation capture and high-throughput chromosome capture assays have shed light on the structural organization of the interphase genome. Functional topologically associating domains (TADs) that constitute the building blocks of genomic organization are disrupted and reconstructed during the cell cycle. Epigenetic memory, as well as the sequence of chromosomes, regulate TAD reconstitution. Sub-TAD domains that are invariant across cell types have been identified, and contacts between these domains, rather than looping, are speculated to drive chromatin folding. Replication domains are established simultaneously with TADs during the cell cycle and the two correlate well in terms of characteristic features, such as lamin association and histone modifications. CCCTC-binding factor (CTCF) and cohesin cooperate across different cell types to regulate genes and genome organization. CTCF elements that demarcate TAD boundaries are commonly disrupted in cancer and promote oncogene activation. Chromatin looping facilitates interactions between distant promoters and enhancers, and the resulting enhanceosome complex promotes gene expression. Deciphering the chromatin tangle requires comprehensive integrative analyses of DNA- and protein-dependent factors that regulate genomic organization.
Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul 143 701, Korea. imcim@konkuk.ac.kr.
Ill-Min
IM
Chung
Department of Pathology, University of Otago, Dunedin 9016, New Zealand. sarada.biotech@gmail.com.
Sarada
S
Ketharnathan
Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul 143 701, Korea. kshkim@konkuk.ac.kr.
Seung-Hyun
SH
Kim
Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul 143 701, Korea. thiruv30@yahoo.com.
Muthu
M
Thiruvengadam
Department of Biochemistry, Periyar University, Salem 636011, Tamil Nadu, India. kavibio91@gmail.com.
Mari Kavitha
MK
Rani
Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul 143 701, Korea. microlabsraj@gmail.com.
Govindasamy
G
Rajakumar
chromatin folding; gene regulation; replication domains; topologically associating domains
Curr Opin Genet Dev. 2016 Feb;36:34-40
27111891
Nature. 2011 Aug 10;476(7361):467-71
21832993
Mol Cell. 2015 Nov 19;60(4):676-84
26527277
Nature. 2011 Oct 12;478(7370):476-82
21993624
Mol Cell Biol. 2013 Jan;33(2):227-36
23109430
Cell Rep. 2016 May 31;15(9):2038-49
27210764
Epigenetics Chromatin. 2014 Jun 16;7:10
25031611
Genome Res. 2006 Oct;16(10):1299-309
16954542
PLoS Genet. 2008 Mar 21;4(3):e1000039
18369458
Front Physiol. 2012 Sep 26;3:368
23055977
Cell. 2014 Dec 18;159(7):1665-80
25497547
Nat Genet. 2006 Nov;38(11):1341-7
17033624
Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8309-14
18550811
Cell Stem Cell. 2016 Feb 4;18(2):262-75
26686465
Genome Res. 2015 Aug;25(8):1104-13
25995270
PLoS Biol. 2005 May;3(5):e157
15839726
Nat Biotechnol. 2006 May;24(5):572-6
16604060
Science. 2015 Feb 27;347(6225):1017-21
25722416
PLoS Pathog. 2011 Aug;7(8):e1002140
21876668
Nature. 2012 Sep 6;489(7414):109-13
22955621
PLoS Comput Biol. 2014 Oct 09;10(10):e1003877
25299688
J Cell Biol. 2004 Sep 13;166(6):775-85
15353545
Mol Syst Biol. 2015 Jan 21;11(1):775
25609649
Nature. 1967 Apr 8;214(5084):208-10
6034232
Cell Res. 2012 Mar;22(3):490-503
22270183
Biochim Biophys Acta. 2012 Jul;1819(7):794-801
22342530
PLoS Biol. 2008 Oct 7;6(10):e245
18842067
Mol Cell. 2010 May 28;38(4):603-13
20513434
Cell. 2014 Oct 9;159(2):374-87
25303531
PLoS Genet. 2015 Jan 08;11(1):e1004897
25569170
Nucleic Acids Res. 2016 May 19;44(9):4222-32
27085808
Nature. 2012 Apr 11;485(7398):376-80
22495300
J Mol Biol. 2014 Oct 9;426(20):3330-41
24905010
Genome Res. 2015 Jul;25(7):958-69
25883320
Trends Genet. 2016 Apr;32(4):225-37
26862051
Genome Biol. 2010;11(11):R110
21078160
J Cell Biol. 2008 Jan 14;180(1):51-65
18195101
Hum Mol Genet. 2013 Feb 1;22(3):544-57
23118352
Cell. 2011 Dec 9;147(6):1283-94
22153073
Cell. 2007 Mar 23;128(6):1231-45
17382889
Science. 2010 May 21;328(5981):1036-40
20378774
J Virol. 2012 Sep;86(17):9454-64
22740398
Curr Opin Genet Dev. 2013 Apr;23(2):124-31
23541525
Cell. 2012 Mar 2;148(5):908-21
22341456
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4424-9
11930003
Nature. 2008 Mar 13;452(7184):243-7
18272965
PLoS Genet. 2013;9(12):e1004018
24385922
Nat Genet. 2006 Nov;38(11):1348-54
17033623
Nat Rev Mol Cell Biol. 2015 Jun;16(6):360-74
25999062
Genome Res. 2014 Mar;24(3):390-400
24398455
Cell. 2008 Feb 8;132(3):422-33
18237772
Nature. 2010 Sep 23;467(7314):430-5
20720539
Cell. 2013 Jan 31;152(3):584-98
23374351
Cell Mol Life Sci. 2015 Jun;72(12):2361-75
25715743
EMBO J. 2008 Feb 20;27(4):654-66
18219272
J Cell Biol. 2008 Sep 22;182(6):1083-97
18809724
Epigenetics Chromatin. 2012 Jan 09;5(1):1
22230046
Curr Opin Cell Biol. 2006 Jun;18(3):231-9
16650748
Nucleic Acids Res. 2014 Jan;42(1):193-204
24071586
Genome Res. 2011 Sep;21(9):1438-49
21750104
Cell. 2015 Aug 13;162(4):900-10
26276636
Genome Res. 2010 Feb;20(2):155-69
19952138
Cell Mol Life Sci. 2016 Aug;73(15):2897-910
27026300
Biophys J. 2009 Feb 18;96(4):1617-28
19217877
Cell. 2013 Jun 6;153(6):1281-95
23706625
J Cell Biol. 2012 Nov 26;199(5):755-70
23166350
Nature. 2012 Apr 11;485(7398):381-5
22495304
Science. 2009 Oct 9;326(5950):289-93
19815776
Bioinformatics. 2016 Jun 1;32(11):1601-9
26315910
Nature. 2008 Feb 14;451(7180):796-801
18235444
Chromosoma. 2004 Jun;112(8):410-23
15197559
Genome Res. 2010 Jun;20(6):761-70
20430782
Genome Res. 2010 May;20(5):578-88
20219941
Cell. 2014 Apr 10;157(2):369-81
24703711
Biochim Biophys Acta. 2009 Jan;1789(1):17-25
18675948