TY  - JOUR
AU  - Schuetzmann, Daniel
AU  - Walter, Carolin
AU  - van Riel, Boet
AU  - Kruse, Sabrina
AU  - König, Thorsten
AU  - Erdmann, Tabea
AU  - Tönges, Alexander
AU  - Bindels, Eric
AU  - Weilemann, Andre
AU  - Gebhard, Claudia
AU  - Wethmar, Klaus
AU  - Perrod, Chiara
AU  - Minderjahn, Julia
AU  - Rehli, Michael
AU  - Delwel, Ruud
AU  - Lenz, Georg
AU  - Gröschel, Stefan
AU  - Dugas, Martin
AU  - Rosenbauer, Frank
TI  - Temporal auto-regulation during human PU.1 locus SubTAD formation.
JO  - Blood
VL  - 132
IS  - 22
SN  - 0006-4971
CY  - Stanford, Calif.
PB  - HighWire Press
M1  - DKFZ-2018-01640
SP  - 2643-2655
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30315124
DO  - DOI:10.1182/blood-2018-02-834721
UR  - https://inrepo02.dkfz.de/record/141106
ER  -