{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:18:08Z","timestamp":1772173088707,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010152","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000}}],"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CBET-1454301"],"award-info":[{"award-number":["CBET-1454301"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["T32EB019941"],"award-info":[{"award-number":["T32EB019941"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Activation of gene expression in response to environmental cues results in substantial phenotypic heterogeneity between cells that can impact a wide range of outcomes including differentiation, viral activation, and drug resistance. An important source of gene expression noise is transcriptional bursting, or the process by which transcripts are produced during infrequent bursts of promoter activity. Chromatin accessibility impacts transcriptional bursting by regulating the assembly of transcription factor and polymerase complexes on promoters, suggesting that the effect of an activating signal on transcriptional noise will depend on the initial chromatin state at the promoter. To explore this possibility, we simulated transcriptional activation using a transcriptional cycling model with three promoter states that represent chromatin remodeling, polymerase binding and pause release. We initiated this model over a large parameter range representing target genes with different chromatin environments, and found that, upon increasing the polymerase pause release rate to activate transcription, changes in gene expression noise varied significantly across initial promoter states. This model captured phenotypic differences in activation of latent HIV viruses integrated at different chromatin locations and mediated by the transcription factor NF-\u03baB. Activating transcription in the model via increasing one or more of the transcript production rates, as occurs following NF-\u03baB activation, reproduced experimentally measured transcript distributions for four different latent HIV viruses, as well as the bimodal pattern of HIV protein expression that leads to a subset of reactivated virus. Importantly, the parameter \u2018activation path\u2019 differentially affected gene expression noise, and ultimately viral activation, in line with experimental observations. This work demonstrates how upstream signaling pathways can be connected to biological processes that underlie transcriptional bursting, resulting in target gene-specific noise profiles following stimulation of a single upstream pathway.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010152","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T17:08:44Z","timestamp":1662743324000},"page":"e1010152","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcription"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7876-4938","authenticated-orcid":true,"given":"M. Elise","family":"Bullock","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9087-0058","authenticated-orcid":true,"given":"Nataly","family":"Moreno-Martinez","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7233-0100","authenticated-orcid":true,"given":"Kathryn","family":"Miller-Jensen","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"pcbi.1010152.ref001","doi-asserted-by":"crossref","first-page":"13176","DOI":"10.1074\/jbc.RA118.001927","article-title":"Transcriptional burst fraction and size dynamics during lens fiber cell differentiation and detailed insights into the denucleation process","volume":"293","author":"S Limi","year":"2018","journal-title":"J Biol Chem"},{"key":"pcbi.1010152.ref002","doi-asserted-by":"crossref","first-page":"8364","DOI":"10.1073\/pnas.1800943115","article-title":"Promoter-mediated diversification of transcriptional 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