TY  - JOUR
AU  - Bender, Alexander
AU  - Boydere, Füsun
AU  - Jayavelu, Ashok Kumar
AU  - Tibello, Alessia
AU  - König, Thorsten
AU  - Aleth, Hanna
AU  - Meyer Zu Hörste, Gerd
AU  - Vogl, Thomas
AU  - Rosenbauer, Frank
TI  - Redistribution of PU.1 partner transcription factor RUNX1 binding secures cell survival during leukemogenesis.
JO  - The EMBO journal
VL  - 43
IS  - 24
SN  - 0261-4189
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DKFZ-2024-02287
SP  - 6291-6309
PY  - 2024
N1  - 2024 Dec;43(24):6291-6309
AB  - Transcription factors (TFs) orchestrating lineage-development often control genes required for cellular survival. However, it is not well understood how cells survive when such TFs are lost, for example in cancer. PU.1 is an essential TF for myeloid fate, and mice with downregulated PU.1 levels develop acute myeloid leukemia (AML). Combining a multi-omics approach with a functional genetic screen, we reveal that PU.1-downregulated cells fundamentally change their survival control from cytokine-driven pathways to overexpression of an autophagy-predominated stem cell gene program, for which we also find evidence in human AML. Control of this program involves redirected chromatin occupancy of the PU.1 partner TF Runx1 to a lineage-inappropriate binding site repertoire. Hence, genomic reallocation of TF binding upon loss of a partner TF can act as a pro-oncogenic failsafe mechanism by sustaining cell survival during leukemogenesis.
KW  - Myeloid Development (Other)
KW  - Myeloid Leukemia (Other)
KW  - PU.1 (Other)
KW  - RUNX1 (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39543396
DO  - DOI:10.1038/s44318-024-00295-y
UR  - https://inrepo02.dkfz.de/record/294462
ER  -