Chromatin variant explained

A chromatin variant 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 sequence.[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]

Notes and 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 . 10.1016/j.gde.2022.101911 . 1879-0380 . 35487182.
  2. Ernst J, Kellis M . Discovery and characterization of chromatin states for systematic annotation of the human genome . Nature Biotechnology . 28 . 8 . 817–25 . August 2010 . 20657582 . 2919626 . 10.1038/nbt.1662 .
  3. Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS, Brown M . 6 . FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription . Cell . 132 . 6 . 958–70 . March 2008 . 18358809 . 2323438 . 10.1016/j.cell.2008.01.018 .
  4. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA, Wang W, Weng Z, Green RD, Crawford GE, Ren B . 6 . Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome . Nature Genetics . 39 . 3 . 311–8 . March 2007 . 17277777 . 10.1038/ng1966 . 1595885 .
  5. Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW, Ching KA, Antosiewicz-Bourget JE, Liu H, Zhang X, Green RD, Lobanenkov VV, Stewart R, Thomson JA, Crawford GE, Kellis M, Ren B . 6 . Histone modifications at human enhancers reflect global cell-type-specific gene expression . Nature . 459 . 7243 . 108–12 . May 2009 . 19295514 . 2910248 . 10.1038/nature07829 . 2009Natur.459..108H .
  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. en. 9. 5. 473–476. 10.1038/nmeth.1937. 1548-7105. 3340533. 22426492.
  7. Deblois G, Tonekaboni SA, Grillo G, Martinez C, Kao YI, Tai F, Ettayebi I, Fortier AM, Savage P, Fedor AN, Liu X, Guilhamon P, Lima-Fernandes E, Murison A, Kuasne H, Ba-Alawi W, Cescon DW, Arrowsmith CH, De Carvalho DD, Haibe-Kains B, Locasale JW, Park M, Lupien M . 6 . Epigenetic Switch-Induced Viral Mimicry Evasion in Chemotherapy-Resistant Breast Cancer . Cancer Discovery . 10 . 9 . 1312–1329 . September 2020 . 32546577 . 10.1158/2159-8290.CD-19-1493 . free .
  8. Timp W, Feinberg AP . Cancer as a dysregulated epigenome allowing cellular growth advantage at the expense of the host . Nature Reviews. Cancer . 13 . 7 . 497–510 . July 2013 . 23760024 . 4636434 . 10.1038/nrc3486 .
  9. McDonald OG, Li X, Saunders T, Tryggvadottir R, Mentch SJ, Warmoes MO, Word AE, Carrer A, Salz TH, Natsume S, Stauffer KM, Makohon-Moore A, Zhong Y, Wu H, Wellen KE, Locasale JW, Iacobuzio-Donahue CA, Feinberg AP . 6 . Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis . Nature Genetics . 49 . 3 . 367–376 . March 2017 . 28092686 . 5695682 . 10.1038/ng.3753 .
  10. Madani Tonekaboni SA, Haibe-Kains B, Lupien M . Large organized chromatin lysine domains help distinguish primitive from differentiated cell populations . Nature Communications . 12 . 1 . 499 . January 2021 . 33479238 . 7820432 . 10.1038/s41467-020-20830-9 . 2021NatCo..12..499M .
  11. Madani Tonekaboni SA, Mazrooei P, Kofia V, Haibe-Kains B, Lupien M . Identifying clusters of cis-regulatory elements underpinning TAD structures and lineage-specific regulatory networks . Genome Research . 29 . 10 . 1733–1743 . October 2019 . 31533978 . 6771399 . 10.1101/gr.248658.119 .
  12. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA . 6 . Super-enhancers in the control of cell identity and disease . Cell . 155 . 4 . 934–47 . November 2013 . 24119843 . 3841062 . 10.1016/j.cell.2013.09.053 .

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