Home > Publications database > Redistribution of PU.1 partner transcription factor RUNX1 binding secures cell survival during leukemogenesis. > print |
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005 | 20241222014504.0 | ||
024 | 7 | _ | |a 10.1038/s44318-024-00295-y |2 doi |
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041 | _ | _ | |a English |
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100 | 1 | _ | |a Bender, Alexander |b 0 |
245 | _ | _ | |a Redistribution of PU.1 partner transcription factor RUNX1 binding secures cell survival during leukemogenesis. |
260 | _ | _ | |a Hoboken, NJ [u.a.] |c 2024 |b Wiley |
336 | 7 | _ | |a article |2 DRIVER |
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336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1734445626_4133 |2 PUB:(DE-HGF) |
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500 | _ | _ | |a 2024 Dec;43(24):6291-6309 |
520 | _ | _ | |a 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. |
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650 | _ | 7 | |a Myeloid Development |2 Other |
650 | _ | 7 | |a Myeloid Leukemia |2 Other |
650 | _ | 7 | |a PU.1 |2 Other |
650 | _ | 7 | |a RUNX1 |2 Other |
700 | 1 | _ | |a Boydere, Füsun |b 1 |
700 | 1 | _ | |a Jayavelu, Ashok Kumar |0 P:(DE-He78)1546aa03aab6491ab3cf01f75ac2b6af |b 2 |u dkfz |
700 | 1 | _ | |a Tibello, Alessia |b 3 |
700 | 1 | _ | |a König, Thorsten |b 4 |
700 | 1 | _ | |a Aleth, Hanna |b 5 |
700 | 1 | _ | |a Meyer Zu Hörste, Gerd |b 6 |
700 | 1 | _ | |a Vogl, Thomas |b 7 |
700 | 1 | _ | |a Rosenbauer, Frank |0 0000-0001-7977-9421 |b 8 |
773 | _ | _ | |a 10.1038/s44318-024-00295-y |0 PERI:(DE-600)1467419-1 |n 24 |p 6291-6309 |t The EMBO journal |v 43 |y 2024 |x 0261-4189 |
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