PU.1 Level-Directed Chromatin Structure Remodeling at the Irf8 Gene Drives Dendritic Cell Commitment

Autoren

Jörg Schönheit
Christiane Kuhl
Marie Luise Gebhardt
Francisco Fernández Klett
Pia Riemke
Marina Scheller
Gang Huang
Ronald Naumann
Achim Leutz
Carol Stocking
Josef Priller
Miguel A Andrade-Navarro
Frank Rosenbauer

DOI

10.1016/j.celrep.2013.04.007

ISSN

2211-1247

Ausgabe der Veröffentlichung

5

Zeitschrift

Cell Reports

Sprache

en

Paginierung

1617 - 1628

Datum der Veröffentlichung

2013

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.celrep.2013.04.007

Datum der Datenerfassung

2022

Titel

PU.1 Level-Directed Chromatin Structure Remodeling at the Irf8 Gene Drives Dendritic Cell Commitment

Ausgabe der Zeitschrift

3

Data source: Crossref

Abstract

Dendritic cells (DCs) are essential regulators of immune responses; however, transcriptional mechanisms that establish DC lineage commitment are poorly defined. Here, we report that the PU.1 transcription factor induces specific remodeling of the higher-order chromatin structure at the interferon regulatory factor 8 (Irf8) gene to initiate DC fate choice. An Irf8 reporter mouse enabled us to pinpoint an initial progenitor stage at which DCs separate from other myeloid lineages in the bone marrow. In the absence of Irf8, this progenitor undergoes DC-to-neutrophil reprogramming, indicating that DC commitment requires an active, Irf8-dependent escape from alternative myeloid lineage potential. Mechanistically, myeloid Irf8 expression depends on high PU.1 levels, resulting in local chromosomal looping and activation of a lineage- and developmental-stage-specific cis-enhancer. These data delineate PU.1 as a concentration-dependent rheostat of myeloid lineage selection by controlling long-distance contacts between regulatory elements and suggest that specific higher-order chromatin remodeling at the Irf8 gene determines DC differentiation.

Addresses

Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.

Autoren

Jörg Schönheit
Christiane Kuhl
Marie Luise Gebhardt
Francisco Fernández Klett
Pia Riemke
Marina Scheller
Gang Huang
Ronald Naumann
Achim Leutz
Carol Stocking
Josef Priller
Miguel A Andrade-Navarro
Frank Rosenbauer

DOI

10.1016/j.celrep.2013.04.007

eISSN

2211-1247

Externe Identifier

PubMed Identifier: 23623495

Open access

false

ISSN

2211-1247

Ausgabe der Veröffentlichung

5

Zeitschrift

Cell reports

Schlüsselwörter

Dendritic Cells
Bone Marrow Cells
Cells, Cultured
Chromatin
Myeloid Cells
Animals
Mice, Inbred C57BL
Mice, Knockout
Humans
Mice
Trans-Activators
Proto-Oncogene Proteins
Cell Differentiation
Chromatin Assembly and Disassembly
Base Sequence
Cell Lineage
Interferon Regulatory Factors
Promoter Regions, Genetic

Sprache

eng

Medium

Print-Electronic

Online publication date

2013

Paginierung

1617 - 1628

Datum der Veröffentlichung

2013

Status

Published

Publisher licence

CC BY-NC-ND

Datum der Datenerfassung

2013

Titel

PU.1 level-directed chromatin structure remodeling at the Irf8 gene drives dendritic cell commitment.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

3

Data source: Europe PubMed Central

Abstract

Dendritic cells (DCs) are essential regulators of immune responses; however, transcriptional mechanisms that establish DC lineage commitment are poorly defined. Here, we report that the PU.1 transcription factor induces specific remodeling of the higher-order chromatin structure at the interferon regulatory factor 8 (Irf8) gene to initiate DC fate choice. An Irf8 reporter mouse enabled us to pinpoint an initial progenitor stage at which DCs separate from other myeloid lineages in the bone marrow. In the absence of Irf8, this progenitor undergoes DC-to-neutrophil reprogramming, indicating that DC commitment requires an active, Irf8-dependent escape from alternative myeloid lineage potential. Mechanistically, myeloid Irf8 expression depends on high PU.1 levels, resulting in local chromosomal looping and activation of a lineage- and developmental-stage-specific cis-enhancer. These data delineate PU.1 as a concentration-dependent rheostat of myeloid lineage selection by controlling long-distance contacts between regulatory elements and suggest that specific higher-order chromatin remodeling at the Irf8 gene determines DC differentiation.

Date of acceptance

2013

Autoren

Jörg Schönheit
Christiane Kuhl
Marie Luise Gebhardt
Francisco Fernández Klett
Pia Riemke
Marina Scheller
Gang Huang
Ronald Naumann
Achim Leutz
Carol Stocking
Josef Priller
Miguel A Andrade-Navarro
Frank Rosenbauer

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/23623495

DOI

10.1016/j.celrep.2013.04.007

eISSN

2211-1247

Ausgabe der Veröffentlichung

5

Zeitschrift

Cell Rep

Schlüsselwörter

Animals
Base Sequence
Bone Marrow Cells
Cell Differentiation
Cell Lineage
Cells, Cultured
Chromatin
Chromatin Assembly and Disassembly
Dendritic Cells
Humans
Interferon Regulatory Factors
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells
Promoter Regions, Genetic
Proto-Oncogene Proteins
Trans-Activators

Sprache

eng

Country

United States

Paginierung

1617 - 1628

PII

S2211-1247(13)00174-5

Datum der Veröffentlichung

2013

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2013

Titel

PU.1 level-directed chromatin structure remodeling at the Irf8 gene drives dendritic cell commitment.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

3

Data source: PubMed

PU.1 Level-Directed Chromatin Structure Remodeling at the Irf8 Gene Drives Dendritic Cell Commitment

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