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Transcription Factor Repertoire of Homeostatic Eosinophilopoiesis

The production of mature eosinophils (Eos) is a tightly orchestrated process with the aim to sustain normal Eos levels in tissues while also maintaining low numbers of these complex and sensitive cells in the blood. To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global a...

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Published in:The Journal of immunology (1950) 2015-09, Vol.195 (6), p.2683-2695
Main Authors: Bouffi, Carine, Kartashov, Andrey V, Schollaert, Kaila L, Chen, Xiaoting, Bacon, W Clark, Weirauch, Matthew T, Barski, Artem, Fulkerson, Patricia C
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cited_by cdi_FETCH-LOGICAL-c495t-1e399a88a8de5db8fcc28d60d46f2c3b96a2323c824fd9053f3ba53d28ec93b13
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container_title The Journal of immunology (1950)
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creator Bouffi, Carine
Kartashov, Andrey V
Schollaert, Kaila L
Chen, Xiaoting
Bacon, W Clark
Weirauch, Matthew T
Barski, Artem
Fulkerson, Patricia C
description The production of mature eosinophils (Eos) is a tightly orchestrated process with the aim to sustain normal Eos levels in tissues while also maintaining low numbers of these complex and sensitive cells in the blood. To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including Eos-lineage commitment and lineage maturation. Our analyses revealed a markedly greater number of transcriptome alterations associated with Eos maturation (1199 genes) than with Eos-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Eos-lineage-committed progenitors (EoPs) were noted to express high levels of granule proteins and contain granules with an ultrastructure distinct from that of mature resting Eos. Our analyses also delineated a 976-gene Eos-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with Eos. EoPs and Eos, but not granulocyte-monocyte progenitors or neutrophils, expressed Helios and Aiolos, members of the Ikaros family of transcription factors, which regulate gene expression via modulation of chromatin structure and DNA accessibility. Epigenetic studies revealed a distinct distribution of active chromatin marks between genes induced with lineage commitment and genes induced with cell maturation during Eos development. In addition, Aiolos and Helios binding sites were significantly enriched in genes expressed by EoPs and Eos with active chromatin, highlighting a potential novel role for Helios and Aiolos in regulating gene expression during Eos development.
doi_str_mv 10.4049/jimmunol.1500510
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subjects Animals
Binding Sites - genetics
Cell Lineage - genetics
Cell Lineage - immunology
Cells, Cultured
Chromatin - genetics
Cytoplasmic Granules - metabolism
DNA-Binding Proteins - genetics
Eosinophils - cytology
Eosinophils - immunology
Gene Expression Regulation - genetics
Granulocyte Precursor Cells
Hematopoiesis - genetics
Hematopoiesis - immunology
Mice
Mice, Inbred BALB C
Trans-Activators - genetics
Transcription Factors - biosynthesis
Transcription Factors - genetics
Transcriptome - genetics
title Transcription Factor Repertoire of Homeostatic Eosinophilopoiesis
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