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dc.contributor.authorBornstein, Chamutal
dc.contributor.authorWinter, Deborah
dc.contributor.authorBarnett-Itzhaki, Zohar
dc.contributor.authorDavid, Eyal
dc.contributor.authorKadri, Sabah
dc.contributor.authorGarber, Manuel
dc.contributor.authorAmit, Ido
dc.date2022-08-11T08:08:36.000
dc.date.accessioned2022-08-23T16:01:05Z
dc.date.available2022-08-23T16:01:05Z
dc.date.issued2014-12-18
dc.date.submitted2018-07-18
dc.identifier.citation<p>Mol Cell. 2014 Dec 18;56(6):749-62. doi: 10.1016/j.molcel.2014.10.014. Epub 2014 Nov 20. <a href="https://doi.org/10.1016/j.molcel.2014.10.014">Link to article on publisher's site</a></p>
dc.identifier.issn1097-2765 (Linking)
dc.identifier.doi10.1016/j.molcel.2014.10.014
dc.identifier.pmid25453760
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31038
dc.description.abstractDuring hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into alternative cell fates are not fully understood. Here, we identify cell-fate-determining transcription factors (TFs) governing dendritic cell (DC) development by annotating the enhancer landscapes of the DC lineage. Combining these analyses with detailed overexpression, knockdown, and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, a pulse of TF expression can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25453760&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412443/
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBioinformatics
dc.subjectCell Biology
dc.subjectComputational Biology
dc.subjectGenetic Phenomena
dc.subjectGenomics
dc.subjectMolecular Biology
dc.titleA negative feedback loop of transcription factors specifies alternative dendritic cell chromatin States
dc.typeArticle
dc.source.journaltitleMolecular cell
dc.source.volume56
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/garber_lab_pubs/6
dc.identifier.contextkey12504420
html.description.abstract<p>During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into alternative cell fates are not fully understood. Here, we identify cell-fate-determining transcription factors (TFs) governing dendritic cell (DC) development by annotating the enhancer landscapes of the DC lineage. Combining these analyses with detailed overexpression, knockdown, and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, a pulse of TF expression can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes.</p>
dc.identifier.submissionpathgarber_lab_pubs/6
dc.contributor.departmentGarber Lab
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.source.pages749-62


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