Chromatin variant

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.{{Cite journal |last=Grillo |first=Giacomo |last2=Lupien |first2=Mathieu |date=June 2022 |title=Cancer-associated chromatin variants uncover the oncogenic role of transposable elements |url=https://pubmed.ncbi.nlm.nih.gov/35487182 |journal=Current Opinion in Genetics & Development |volume=74 |pages=101911 |doi=10.1016/j.gde.2022.101911 |issn=1879-0380 |pmid=35487182}} Chromatin variants range in sizes. The smallest chromatin variants cover a few hundred DNA base pairs, such as seen at promoters, enhancers or insulators.{{cite journal | vauthors = Ernst J, Kellis M | title = Discovery and characterization of chromatin states for systematic annotation of the human genome | journal = Nature Biotechnology | volume = 28 | issue = 8 | pages = 817–25 | date = August 2010 | pmid = 20657582 | pmc = 2919626 | doi = 10.1038/nbt.1662 }}{{cite journal | vauthors = Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS, Brown M | display-authors = 6 | title = FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription | journal = Cell | volume = 132 | issue = 6 | pages = 958–70 | date = March 2008 | pmid = 18358809 | pmc = 2323438 | doi = 10.1016/j.cell.2008.01.018 }}{{cite journal | vauthors = 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 | display-authors = 6 | title = Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome | journal = Nature Genetics | volume = 39 | issue = 3 | pages = 311–8 | date = March 2007 | pmid = 17277777 | doi = 10.1038/ng1966 | s2cid = 1595885 }}{{cite journal | vauthors = 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 | display-authors = 6 | title = Histone modifications at human enhancers reflect global cell-type-specific gene expression | journal = Nature | volume = 459 | issue = 7243 | pages = 108–12 | date = May 2009 | pmid = 19295514 | pmc = 2910248 | doi = 10.1038/nature07829 | bibcode = 2009Natur.459..108H }}{{Cite journal|last1=Hoffman|first1=Michael M.|last2=Buske|first2=Orion J.|last3=Wang|first3=Jie|last4=Weng|first4=Zhiping|last5=Bilmes|first5=Jeff A.|last6=Noble|first6=William Stafford|date=May 2012|title=Unsupervised pattern discovery in human chromatin structure through genomic segmentation|journal=Nature Methods|language=en|volume=9|issue=5|pages=473–476|doi=10.1038/nmeth.1937|issn=1548-7105|pmc=3340533|pmid=22426492}} The largest chromatin variants capture a few thousand DNA base pairs, such as seen at Large Organized Chromatin Lysine domains (LOCKs){{cite journal | vauthors = 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 | display-authors = 6 | title = Epigenetic Switch-Induced Viral Mimicry Evasion in Chemotherapy-Resistant Breast Cancer | journal = Cancer Discovery | volume = 10 | issue = 9 | pages = 1312–1329 | date = September 2020 | pmid = 32546577 | doi = 10.1158/2159-8290.CD-19-1493 | doi-access = free }}{{cite journal | vauthors = Timp W, Feinberg AP | title = Cancer as a dysregulated epigenome allowing cellular growth advantage at the expense of the host | journal = Nature Reviews. Cancer | volume = 13 | issue = 7 | pages = 497–510 | date = July 2013 | pmid = 23760024 | pmc = 4636434 | doi = 10.1038/nrc3486 }}{{cite journal | vauthors = 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 | display-authors = 6 | title = Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis | journal = Nature Genetics | volume = 49 | issue = 3 | pages = 367–376 | date = March 2017 | pmid = 28092686 | pmc = 5695682 | doi = 10.1038/ng.3753 }}{{cite journal | vauthors = Madani Tonekaboni SA, Haibe-Kains B, Lupien M | title = Large organized chromatin lysine domains help distinguish primitive from differentiated cell populations | journal = Nature Communications | volume = 12 | issue = 1 | pages = 499 | date = January 2021 | pmid = 33479238 | pmc = 7820432 | doi = 10.1038/s41467-020-20830-9 | bibcode = 2021NatCo..12..499M }} and Clusters Of Cis-Regulatory Elements (COREs), such as super-enhancer.{{cite journal | vauthors = Madani Tonekaboni SA, Mazrooei P, Kofia V, Haibe-Kains B, Lupien M | title = Identifying clusters of cis-regulatory elements underpinning TAD structures and lineage-specific regulatory networks | journal = Genome Research | volume = 29 | issue = 10 | pages = 1733–1743 | date = October 2019 | pmid = 31533978 | pmc = 6771399 | doi = 10.1101/gr.248658.119 }}{{cite journal | vauthors = Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA | display-authors = 6 | title = Super-enhancers in the control of cell identity and disease | journal = Cell | volume = 155 | issue = 4 | pages = 934–47 | date = November 2013 | pmid = 24119843 | pmc = 3841062 | doi = 10.1016/j.cell.2013.09.053 }}