Chromatin variant

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A chromatin variant (also known as an epigenetic lesion, epimutation or epigenetic alteration) corresponds to a section of the genome that differs in chromatin states across cell types/states within an individual (intra-individual) or between individuals for a given cell type/state (inter-individual). Chromatin variants distinguish DNA sequences that differ in their function in one cell type/state versus another. Chromatin variants are found across the genome, inclusive of repetitive and non-repetitive DNA sequences. [1] Chromatin variants range in sizes. The smallest chromatin variants cover a few hundred DNA base pairs, such as seen at promoters, enhancers or insulators. [2] [3] [4] [5] [6] The largest chromatin variants capture a few thousand DNA base pairs, such as seen at Large Organized Chromatin Lysine domains (LOCKs) [7] [8] [9] [10] and Clusters Of Cis-Regulatory Elements (COREs), such as super-enhancer. [11] [12]

References

  1. ↑ Grillo, Giacomo; Lupien, Mathieu (June 2022). "Cancer-associated chromatin variants uncover the oncogenic role of transposable elements". Current Opinion in Genetics & Development. 74 101911. doi:10.1016/j.gde.2022.101911. ISSN   1879-0380. PMID   35487182.
  2. ↑ Ernst J, Kellis M (August 2010). "Discovery and characterization of chromatin states for systematic annotation of the human genome". Nature Biotechnology. 28 (8): 817–25. doi:10.1038/nbt.1662. PMC   2919626 . PMID   20657582.
  3. ↑ Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, et al. (March 2008). "FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription". Cell. 132 (6): 958–70. doi:10.1016/j.cell.2008.01.018. PMC   2323438 . PMID   18358809.
  4. ↑ Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, et al. (March 2007). "Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome". Nature Genetics. 39 (3): 311–8. doi:10.1038/ng1966. PMID   17277777. S2CID   1595885.
  5. ↑ Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, et al. (May 2009). "Histone modifications at human enhancers reflect global cell-type-specific gene expression". Nature. 459 (7243): 108–12. Bibcode:2009Natur.459..108H. doi:10.1038/nature07829. PMC   2910248 . PMID   19295514.
  6. ↑ Hoffman, Michael M.; Buske, Orion J.; Wang, Jie; Weng, Zhiping; Bilmes, Jeff A.; Noble, William Stafford (May 2012). "Unsupervised pattern discovery in human chromatin structure through genomic segmentation". Nature Methods. 9 (5): 473–476. doi:10.1038/nmeth.1937. ISSN   1548-7105. PMC   3340533 . PMID   22426492.
  7. ↑ Deblois G, Tonekaboni SA, Grillo G, Martinez C, Kao YI, Tai F, et al. (September 2020). "Epigenetic Switch-Induced Viral Mimicry Evasion in Chemotherapy-Resistant Breast Cancer". Cancer Discovery. 10 (9): 1312–1329. doi: 10.1158/2159-8290.CD-19-1493 . PMID   32546577.
  8. ↑ Timp W, Feinberg AP (July 2013). "Cancer as a dysregulated epigenome allowing cellular growth advantage at the expense of the host". Nature Reviews. Cancer. 13 (7): 497–510. doi:10.1038/nrc3486. PMC   4636434 . PMID   23760024.
  9. ↑ McDonald OG, Li X, Saunders T, Tryggvadottir R, Mentch SJ, Warmoes MO, et al. (March 2017). "Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis". Nature Genetics. 49 (3): 367–376. doi:10.1038/ng.3753. PMC   5695682 . PMID   28092686.
  10. ↑ Madani Tonekaboni SA, Haibe-Kains B, Lupien M (January 2021). "Large organized chromatin lysine domains help distinguish primitive from differentiated cell populations". Nature Communications. 12 (1) 499. Bibcode:2021NatCo..12..499M. doi:10.1038/s41467-020-20830-9. PMC   7820432 . PMID   33479238.
  11. ↑ Madani Tonekaboni SA, Mazrooei P, Kofia V, Haibe-Kains B, Lupien M (October 2019). "Identifying clusters of cis-regulatory elements underpinning TAD structures and lineage-specific regulatory networks". Genome Research. 29 (10): 1733–1743. doi:10.1101/gr.248658.119. PMC   6771399 . PMID   31533978.
  12. ↑ Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, et al. (November 2013). "Super-enhancers in the control of cell identity and disease". Cell. 155 (4): 934–47. doi:10.1016/j.cell.2013.09.053. PMC   3841062 . PMID   24119843.
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