PMID- 23623495
OWN - NLM
STAT- MEDLINE
DCOM- 20131216
LR  - 20130603
IS  - 2211-1247 (Electronic)
VI  - 3
IP  - 5
DP  - 2013 May 30
TI  - PU.1 level-directed chromatin structure remodeling at the Irf8 gene drives 
      dendritic cell commitment.
PG  - 1617-28
LID - S2211-1247(13)00174-5 [pii]
LID - 10.1016/j.celrep.2013.04.007 [doi]
AB  - 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.
CI  - Copyright (c) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Schonheit, Jorg
AU  - Schonheit J
AD  - Max Delbruck Center for Molecular Medicine, 13125 Berlin, Germany.
FAU - Kuhl, Christiane
AU  - Kuhl C
FAU - Gebhardt, Marie Luise
AU  - Gebhardt ML
FAU - Klett, Francisco Fernandez
AU  - Klett FF
FAU - Riemke, Pia
AU  - Riemke P
FAU - Scheller, Marina
AU  - Scheller M
FAU - Huang, Gang
AU  - Huang G
FAU - Naumann, Ronald
AU  - Naumann R
FAU - Leutz, Achim
AU  - Leutz A
FAU - Stocking, Carol
AU  - Stocking C
FAU - Priller, Josef
AU  - Priller J
FAU - Andrade-Navarro, Miguel A
AU  - Andrade-Navarro MA
FAU - Rosenbauer, Frank
AU  - Rosenbauer F
LA  - eng
SI  - GEO/GSE45467
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130425
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Chromatin)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (interferon regulatory factor-8)
RN  - 0 (proto-oncogene protein Spi-1)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Cells/cytology
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cells, Cultured
MH  - Chromatin/*metabolism
MH  - *Chromatin Assembly and Disassembly
MH  - Dendritic Cells/*cytology/metabolism
MH  - Humans
MH  - Interferon Regulatory Factors/*genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Cells/cytology
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/chemistry/*metabolism
MH  - Trans-Activators/chemistry/*metabolism
EDAT- 2013/04/30 06:00
MHDA- 2013/12/18 06:00
CRDT- 2013/04/30 06:00
PHST- 2012/05/14 00:00 [received]
PHST- 2012/11/23 00:00 [revised]
PHST- 2013/04/08 00:00 [accepted]
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
AID - S2211-1247(13)00174-5 [pii]
AID - 10.1016/j.celrep.2013.04.007 [doi]
PST - ppublish
SO  - Cell Rep. 2013 May 30;3(5):1617-28. doi: 10.1016/j.celrep.2013.04.007. Epub 2013 
      Apr 25.