Functional human genes typically exhibit epigenetic conservation.

Recent DepMap CRISPR-Cas9 single gene disruptions have identified genes more essential to proliferation in tissue culture. It would be valuable to translate these finding with measurements more practical for human tissues. Here we show that DepMap essential genes and other literature curated functio...

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Autores principales: Daniel Rud, Paul Marjoram, Kimberly Siegmund, Darryl Shibata
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Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/dd5e8a0b733444d29d5c1894c5fc6331
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spelling oai:doaj.org-article:dd5e8a0b733444d29d5c1894c5fc63312021-12-02T20:08:17ZFunctional human genes typically exhibit epigenetic conservation.1932-620310.1371/journal.pone.0253250https://doaj.org/article/dd5e8a0b733444d29d5c1894c5fc63312021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253250https://doaj.org/toc/1932-6203Recent DepMap CRISPR-Cas9 single gene disruptions have identified genes more essential to proliferation in tissue culture. It would be valuable to translate these finding with measurements more practical for human tissues. Here we show that DepMap essential genes and other literature curated functional genes exhibit cell-specific preferential epigenetic conservation when DNA methylation measurements are compared between replicate cell lines and between intestinal crypts from the same individual. Culture experiments indicate that epigenetic drift accumulates through time with smaller differences in more functional genes. In NCI-60 cell lines, greater targeted gene conservation correlated with greater drug sensitivity. These studies indicate that two measurements separated in time allow normal or neoplastic cells to signal through conservation which human genes are more essential to their survival in vitro or in vivo.Daniel RudPaul MarjoramKimberly SiegmundDarryl ShibataPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0253250 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Daniel Rud
Paul Marjoram
Kimberly Siegmund
Darryl Shibata
Functional human genes typically exhibit epigenetic conservation.
description Recent DepMap CRISPR-Cas9 single gene disruptions have identified genes more essential to proliferation in tissue culture. It would be valuable to translate these finding with measurements more practical for human tissues. Here we show that DepMap essential genes and other literature curated functional genes exhibit cell-specific preferential epigenetic conservation when DNA methylation measurements are compared between replicate cell lines and between intestinal crypts from the same individual. Culture experiments indicate that epigenetic drift accumulates through time with smaller differences in more functional genes. In NCI-60 cell lines, greater targeted gene conservation correlated with greater drug sensitivity. These studies indicate that two measurements separated in time allow normal or neoplastic cells to signal through conservation which human genes are more essential to their survival in vitro or in vivo.
format article
author Daniel Rud
Paul Marjoram
Kimberly Siegmund
Darryl Shibata
author_facet Daniel Rud
Paul Marjoram
Kimberly Siegmund
Darryl Shibata
author_sort Daniel Rud
title Functional human genes typically exhibit epigenetic conservation.
title_short Functional human genes typically exhibit epigenetic conservation.
title_full Functional human genes typically exhibit epigenetic conservation.
title_fullStr Functional human genes typically exhibit epigenetic conservation.
title_full_unstemmed Functional human genes typically exhibit epigenetic conservation.
title_sort functional human genes typically exhibit epigenetic conservation.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/dd5e8a0b733444d29d5c1894c5fc6331
work_keys_str_mv AT danielrud functionalhumangenestypicallyexhibitepigeneticconservation
AT paulmarjoram functionalhumangenestypicallyexhibitepigeneticconservation
AT kimberlysiegmund functionalhumangenestypicallyexhibitepigeneticconservation
AT darrylshibata functionalhumangenestypicallyexhibitepigeneticconservation
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