TY  - JOUR
A1  - Debaize, Lydie
A1  - Jakobczyk, Hélène
A1  - Avner, Stéphane
A1  - Gaudichon, Jérémie
A1  - Rio, Anne-Gaëlle
A1  - Sérandour, Aurélien A.
A1  - Dorsheimer, Lena
A1  - Chalmel, Frédéric
A1  - Carroll, Jason S.
A1  - Zörnig, Martin
A1  - Rieger, Michael A.
A1  - Delalande, Olivier
A1  - Salbert, Gilles
A1  - Galibert, Marie-Dominique
A1  - Gandemer, Virginie
A1  - Troadec, Marie-Bérengère
T1  - Interplay between transcription regulators RUNX1 and FUBP1 activates an enhancer of the oncogene c-KIT and amplifies cell proliferation
T2  - Nucleic acids research
N2  - Runt-related transcription factor 1 (RUNX1) is a well-known master regulator of hematopoietic lineages but its mechanisms of action are still not fully understood. Here, we found that RUNX1 localizes on active chromatin together with Far Upstream Binding Protein 1 (FUBP1) in human B-cell precursor lymphoblasts, and that both factors interact in the same transcriptional regulatory complex. RUNX1 and FUBP1 chromatin localization identified c-KIT as a common target gene. We characterized two regulatory regions, at +700 bp and +30 kb within the first intron of c-KIT, bound by both RUNX1 and FUBP1, and that present active histone marks. Based on these regions, we proposed a novel FUBP1 FUSE-like DNA-binding sequence on the +30 kb enhancer. We demonstrated that FUBP1 and RUNX1 cooperate for the regulation of the expression of the oncogene c-KIT. Notably, upregulation of c-KIT expression by FUBP1 and RUNX1 promotes cell proliferation and renders cells more resistant to the c-KIT inhibitor imatinib mesylate, a common therapeutic drug. These results reveal a new mechanism of action of RUNX1 that implicates FUBP1, as a facilitator, to trigger transcriptional regulation of c-KIT and to regulate cell proliferation. Deregulation of this regulatory mechanism may explain some oncogenic function of RUNX1 and FUBP1.
KW  - Gene Regulation
KW  - Chromatin and Epigenetics
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48578
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-485781
SN  - 1362-4962
SN  - 0305-1048
SN  - 1362-4954
N1  - This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
VL  - 46
IS  - 21
SP  - 11214
EP  - 11228
PB  - Oxford Univ. Press
CY  - Oxford
ER  -