HiTAD: Detecting the Structural and Functional Hierarchies of Topologically Associating Domains from Chromatin Interactions

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2017 Oct 5

PMID 28977529

Citations 42

Authors

Xiao-Tao Wang

Wang Cui

Cheng Peng

Affiliations

Soon will be listed here.

Abstract

A current question in the high-order organization of chromatin is whether topologically associating domains (TADs) are distinct from other hierarchical chromatin domains. However, due to the unclear TAD definition in tradition, the structural and functional uniqueness of TAD is not well studied. In this work, we refined TAD definition by further constraining TADs to the optimal separation on global intra-chromosomal interactions. Inspired by this constraint, we developed a novel method, called HiTAD, to detect hierarchical TADs from Hi-C chromatin interactions. HiTAD performs well in domain sensitivity, replicate reproducibility and inter cell-type conservation. With a novel domain-based alignment proposed by us, we defined several types of hierarchical TAD changes which were not systematically studied previously, and subsequently used them to reveal that TADs and sub-TADs differed statistically in correlating chromosomal compartment, replication timing and gene transcription. Finally, our work also has the implication that the refinement of TAD definition could be achieved by only utilizing chromatin interactions, at least in part. HiTAD is freely available online.

Citing Articles

Epigenomic and 3D genomic mapping reveals developmental dynamics and subgenomic asymmetry of transcriptional regulatory architecture in allotetraploid cotton.

Huang X, Wang Y, Zhang S, Pei L, You J, Long Y Nat Commun. 2024; 15(1):10721.

PMID: 39730363 PMC: 11680999. DOI: 10.1038/s41467-024-55309-4.

LDB1 establishes multi-enhancer networks to regulate gene expression.

Aboreden N, Lam J, Goel V, Wang S, Wang X, Midla S Mol Cell. 2024; 85(2):376-393.e9.

PMID: 39721581 PMC: 11741933. DOI: 10.1016/j.molcel.2024.11.037.

An integrative TAD catalog in lymphoblastoid cell lines discloses the functional impact of deletions and insertions in human genomes.

Li C, Bonder M, Syed S, Jensen M, Gerstein M, Zody M Genome Res. 2024; 34(12):2304-2318.

PMID: 39638559 PMC: 11694747. DOI: 10.1101/gr.279419.124.

Obtention of viable cell suspensions from breast cancer tumor biopsies for 3D chromatin conformation and single-cell transcriptome analysis.

Stephenson-Gussinye A, Rendon-Bautista L, Ruiz-Medina B, Blanco-Olais E, Perez-Molina R, Marcial-Medina C Front Mol Biosci. 2024; 11:1420308.

PMID: 39239354 PMC: 11375512. DOI: 10.3389/fmolb.2024.1420308.

LDB1 establishes multi-enhancer networks to regulate gene expression.

Aboreden N, Lam J, Goel V, Wang S, Wang X, Midla S bioRxiv. 2024; .

PMID: 39229045 PMC: 11370584. DOI: 10.1101/2024.08.23.609430.

References

Chen J, Hero 3rd A, Rajapakse I . Spectral identification of topological domains. Bioinformatics. 2016; 32(14):2151-8. PMC: 4937202. DOI: 10.1093/bioinformatics/btw221. View

Dostie J, Richmond T, Arnaout R, Selzer R, Lee W, Honan T . Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res. 2006; 16(10):1299-309. PMC: 1581439. DOI: 10.1101/gr.5571506. View

Rao S, Huntley M, Durand N, Stamenova E, Bochkov I, Robinson J . A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014; 159(7):1665-80. PMC: 5635824. DOI: 10.1016/j.cell.2014.11.021. View

Zhao Z, Tavoosidana G, Sjolinder M, Gondor A, Mariano P, Wang S . Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nat Genet. 2006; 38(11):1341-7. DOI: 10.1038/ng1891. View

Wang X, Dong P, Zhang H, Peng C . Structural heterogeneity and functional diversity of topologically associating domains in mammalian genomes. Nucleic Acids Res. 2015; 43(15):7237-46. PMC: 4551926. DOI: 10.1093/nar/gkv684. View

Jin F, Li Y, Dixon J, Selvaraj S, Ye Z, Lee A . A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature. 2013; 503(7475):290-4. PMC: 3838900. DOI: 10.1038/nature12644. View

Andrey G, Montavon T, Mascrez B, Gonzalez F, Noordermeer D, Leleu M . A switch between topological domains underlies HoxD genes collinearity in mouse limbs. Science. 2013; 340(6137):1234167. DOI: 10.1126/science.1234167. View

Imakaev M, Fudenberg G, McCord R, Naumova N, Goloborodko A, Lajoie B . Iterative correction of Hi-C data reveals hallmarks of chromosome organization. Nat Methods. 2012; 9(10):999-1003. PMC: 3816492. DOI: 10.1038/nmeth.2148. View

Flavahan W, Drier Y, Liau B, Gillespie S, Venteicher A, Stemmer-Rachamimov A . Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature. 2015; 529(7584):110-4. PMC: 4831574. DOI: 10.1038/nature16490. View

10.

Sanyal A, Lajoie B, Jain G, Dekker J . The long-range interaction landscape of gene promoters. Nature. 2012; 489(7414):109-13. PMC: 3555147. DOI: 10.1038/nature11279. View

11.

Hnisz D, Weintraub A, Day D, Valton A, Bak R, Li C . Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science. 2016; 351(6280):1454-1458. PMC: 4884612. DOI: 10.1126/science.aad9024. View

12.

Gomez-Marin C, Tena J, Acemel R, Lopez-Mayorga M, Naranjo S, de la Calle-Mustienes E . Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders. Proc Natl Acad Sci U S A. 2015; 112(24):7542-7. PMC: 4475986. DOI: 10.1073/pnas.1505463112. View

13.

Pope B, Ryba T, Dileep V, Yue F, Wu W, Denas O . Topologically associating domains are stable units of replication-timing regulation. Nature. 2014; 515(7527):402-5. PMC: 4251741. DOI: 10.1038/nature13986. View

14.

Fullwood M, Liu M, Pan Y, Liu J, Xu H, Mohamed Y . An oestrogen-receptor-alpha-bound human chromatin interactome. Nature. 2009; 462(7269):58-64. PMC: 2774924. DOI: 10.1038/nature08497. View

15.

Levy-Leduc C, Delattre M, Mary-Huard T, Robin S . Two-dimensional segmentation for analyzing Hi-C data. Bioinformatics. 2014; 30(17):i386-92. PMC: 4147896. DOI: 10.1093/bioinformatics/btu443. View

16.

Busslinger G, Stocsits R, van der Lelij P, Axelsson E, Tedeschi A, Galjart N . Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl. Nature. 2017; 544(7651):503-507. PMC: 6080695. DOI: 10.1038/nature22063. View

17.

Dixon J, Selvaraj S, Yue F, Kim A, Li Y, Shen Y . Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012; 485(7398):376-80. PMC: 3356448. DOI: 10.1038/nature11082. View

18.

. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012; 489(7414):57-74. PMC: 3439153. DOI: 10.1038/nature11247. View

19.

Haddad N, Vaillant C, Jost D . IC-Finder: inferring robustly the hierarchical organization of chromatin folding. Nucleic Acids Res. 2017; 45(10):e81. PMC: 5449546. DOI: 10.1093/nar/gkx036. View

20.

Dryden N, Broome L, Dudbridge F, Johnson N, Orr N, Schoenfelder S . Unbiased analysis of potential targets of breast cancer susceptibility loci by Capture Hi-C. Genome Res. 2014; 24(11):1854-68. PMC: 4216926. DOI: 10.1101/gr.175034.114. View