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@ARTICLE{Schuetzmann:141106,
author = {D. Schuetzmann and C. Walter and B. van Riel and S.
Kruse$^*$ and T. König and T. Erdmann and A. Tönges and E.
Bindels and A. Weilemann and C. Gebhard and K. Wethmar and
C. Perrod and J. Minderjahn and M. Rehli and R. Delwel and
G. Lenz and S. Gröschel and M. Dugas and F. Rosenbauer},
title = {{T}emporal auto-regulation during human {PU}.1 locus
{S}ub{TAD} formation.},
journal = {Blood},
volume = {132},
number = {22},
issn = {0006-4971},
address = {Stanford, Calif.},
publisher = {HighWire Press},
reportid = {DKFZ-2018-01640},
pages = {2643-2655},
year = {2018},
abstract = {Epigenetic control of gene expression occurs within
discrete spatial chromosomal units called topologically
associating domains (TADs), but the exact spatial
requirements of most genes are unknown; this is of
particular interest for genes involved in cancer. We
therefore applied high-resolution chromosomal conformation
capture-sequencing to map the three-dimensional (3D)
organization of the human locus encoding the key myeloid
transcription factor PU.1 in healthy monocytes and acute
myeloid leukemia (AML) cells. We identified a dynamic ~75kb
unit (SubTAD) as the genomic region in which spatial
interactions between PU.1 gene regulatory elements occur
during myeloid differentiation and are interrupted in AML.
Within this SubTAD, proper initiation of the spatial
chromosomal interactions requires PU.1 auto-regulation and
recruitment of the chromatin-adaptor protein LDB1 (LIM
domain-binding protein 1). However, once these spatial
interactions have occurred, LDB1 stabilizes them
independently of PU.1 auto-regulation. Thus, our data
support that PU.1 auto-regulates its expression in a
hit-and-run manner by initiating stable chromosomal loops
that result in a transcriptionally active chromatin
architecture.},
cin = {G240 / L101},
ddc = {610},
cid = {I:(DE-He78)G240-20160331 / I:(DE-He78)L101-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30315124},
doi = {10.1182/blood-2018-02-834721},
url = {https://inrepo02.dkfz.de/record/141106},
}