Molecular architecture of transcription factor hotspots in early adipogenesis
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Molecular architecture of transcription factor hotspots in early adipogenesis. / Siersbæk, Rasmus; Baek, Songjoon; Rabiee, Atefeh; Nielsen, Ronni; Traynor, Sofie; Clarke, Nicholas; Sandelin, Albin Gustav; Jensen, Ole N.; Sung, Myong-Hee; Hager, Gordon L.; Mandrup, Susanne.
I: Cell Reports, Bind 7, Nr. 5, 2014, s. 1434-1442.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Molecular architecture of transcription factor hotspots in early adipogenesis
AU - Siersbæk, Rasmus
AU - Baek, Songjoon
AU - Rabiee, Atefeh
AU - Nielsen, Ronni
AU - Traynor, Sofie
AU - Clarke, Nicholas
AU - Sandelin, Albin Gustav
AU - Jensen, Ole N.
AU - Sung, Myong-Hee
AU - Hager, Gordon L.
AU - Mandrup, Susanne
N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2014
Y1 - 2014
N2 - Transcription factors have recently been shown to colocalize in hotspot regions of the genome, which are further clustered into super-enhancers. However, the detailed molecular organization of transcription factors at hotspot regions is poorly defined. Here, we have used digital genomic footprinting to precisely define factor localization at a genome-wide level during the early phase of 3T3-L1 adipocyte differentiation, which allows us to obtain detailed molecular insight into how transcription factors target hotspots. We demonstrate the formation of ATF-C/EBP heterodimers at a composite motif on chromatin, and we suggest that this may be a general mechanism for integrating external signals on chromatin. Furthermore, we find evidence of extensive recruitment of transcription factors to hotspots through alternative mechanisms not involving their known motifs and demonstrate that these alternative binding events are functionally important for hotspot formation and activity. Taken together, these findings provide a framework for understanding transcription factor cooperativity in hotspots.
AB - Transcription factors have recently been shown to colocalize in hotspot regions of the genome, which are further clustered into super-enhancers. However, the detailed molecular organization of transcription factors at hotspot regions is poorly defined. Here, we have used digital genomic footprinting to precisely define factor localization at a genome-wide level during the early phase of 3T3-L1 adipocyte differentiation, which allows us to obtain detailed molecular insight into how transcription factors target hotspots. We demonstrate the formation of ATF-C/EBP heterodimers at a composite motif on chromatin, and we suggest that this may be a general mechanism for integrating external signals on chromatin. Furthermore, we find evidence of extensive recruitment of transcription factors to hotspots through alternative mechanisms not involving their known motifs and demonstrate that these alternative binding events are functionally important for hotspot formation and activity. Taken together, these findings provide a framework for understanding transcription factor cooperativity in hotspots.
U2 - 10.1016/j.celrep.2014.04.043
DO - 10.1016/j.celrep.2014.04.043
M3 - Journal article
C2 - 24857666
VL - 7
SP - 1434
EP - 1442
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 5
ER -
ID: 113242052