کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1996312 1065456 2014 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Negative Feedback Loop of Transcription Factors Specifies Alternative Dendritic Cell Chromatin States
ترجمه فارسی عنوان
یک حلقه بازخورد منفی عوامل رونویسی مشخص کننده حالت های کروماتین سلول های دندریتیک جایگزین است
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی


• Differential usage of enhancers regulates distinct expression in moDCs and pDCs
• Alternative chromatin states of DC subtypes are established by Irf8 and Cebpb
• Transcription factor regulatory circuits maintain differential DC fates
• Example of the design principles in establishment of alternative epigenomic states

SummaryDuring 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 56, Issue 6, 18 December 2014, Pages 749–762
نویسندگان
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