The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts
Open accessAbstract
Our current understanding of how DNA is packed in the nucleus is most accurate at the fine scale of individual nucleosomes and at the large scale of chromosome territories. However, accurate modeling of DNA architecture at the intermediate scale of ∼50 kb–10 Mb is crucial for identifying functional interactions among regulatory elements and their target promoters. We describe a method,Fit-Hi-C, that assigns statistical confidence estimates to mid-range intra-chromosomal contacts by jointly modeling the random polymer looping effect and previously observed technical biases in Hi-C data sets. We demonstrate that our proposed approach computes accurate empirical null models of contact probability without any distribution assumption, corrects for binning artifacts, and provides improved statistical power relative to a previously described method. High-confidence contacts identified by Fit-Hi-C preferentially link expressed gene promoters to active enhancers identified by chromatin signatures in human embryonic stem cells (ESCs), capture 77% of RNA polymerase II-mediated enhancer-promoter interactions identified using ChIA-PET in mouse ESCs, and confirm previously validated, cell line-specific interactions in mouse cortex cells. We observe that insulators and heterochromatin regions are hubs for high-confidence contacts, while promoters and strong enhancers are involved in fewer contacts. We also observe that binding peaks of master pluripotency factors such as NANOG and POU5F1 are highly enriched in high-confidence contacts for human ESCs. Furthermore, we show that pairs of loci linked by high-confidence contacts exhibit similar replication timing in human and mouse ESCs and preferentially lie within the boundaries of topological domains for human and mouse cell lines.
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Cites
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Iterative correction of Hi-C data reveals hallmarks of chromosome organization
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A map of the cis-regulatory sequences in the mouse genome
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“Both of the genes transcribed from these promoters ( Gucy1a3 , Gucy1b3 ), as well as a third gene that is 212 kb downstream from the Gucy1a3 promoter ( Map9 ), exhibit cortex-specific expression (Shen et al. 2012).”
BackgroundMethodResultInfluentialLooping and Interaction between Hypersensitive Sites in the Active β-globin Locus
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Cited by
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212
HiChIP: efficient and sensitive analysis of protein-directed genome architecture
Mumbach, M. R., Rubin, A. J., Flynn, R. A., Dai, C., Khavari, P. A., Greenleaf, W. J., & Chang, H. Y. (2016) · Nature Methods · doi:10.1038/nmeth.3999 · Cited by 1,139
Satpathy, A. T., Granja, J. M., Yost, K. E., Qi, Y., Meschi, F., McDermott, G. P., Olsen, B. N., Mumbach, M. R., Pierce, S. E., Corces, M. R., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0206-z · Cited by 980
A compendium of chromatin contact maps reveals spatially active regions in the human genome
Schmitt, A. D., Hu, M., Jung, I., Xu, Z., Qiu, Y., Tan, C. L., Li, Y., Lin, S., Lin, Y., Barr, C. L., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.061 · Cited by 866
HiCRep: assessing the reproducibility of Hi-C data using a stratum-adjusted correlation coefficient
Yang, T., Zhang, F., Yardımcı, G. G., Song, F., Hardison, R. C., Noble, W. S., Yue, F., & Li, Q. (2017) · Genome Research · doi:10.1101/gr.220640.117 · Cited by 533
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Metadata
- Authors
- Ay, F., Bailey, T. L., & Noble, W. S.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2014-02-05
- Volume
- 24
- Issue
- 6
- Pages
- 999-1011
- ISSN
- 1088-9051 (ISSN-L)
- OpenAlex
- W2142270559
- Cited by
- 491
- References
- 8
- Type
- posted content
- Language
- en
- Open access
- bronze
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