DeSUMOylation of chromatin-bound proteins limits the rapid transcriptional reprogramming induced by daunorubicin in acute myeloid leukemias
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DeSUMOylation of chromatin-bound proteins limits the rapid transcriptional reprogramming induced by daunorubicin in acute myeloid leukemias. / Boulanger, Mathias; Aqrouq, Mays; Tempé, Denis; Kifagi, Chamseddine; Ristic, Marko; Akl, Dana; Hallal, Rawan; Carusi, Aude; Gabellier, Ludovic; de Toledo, Marion; Sigurdsson, Jon-Otti; Kaoma, Tony; Andrieu-Soler, Charlotte; Forné, Thierry; Soler, Eric; Hicheri, Yosr; Gueret, Elise; Vallar, Laurent; Olsen, Jesper V.; Cartron, Guillaume; Piechaczyk, Marc; Bossis, Guillaume.
In: Nucleic Acids Research, Vol. 51, No. 16, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - DeSUMOylation of chromatin-bound proteins limits the rapid transcriptional reprogramming induced by daunorubicin in acute myeloid leukemias
AU - Boulanger, Mathias
AU - Aqrouq, Mays
AU - Tempé, Denis
AU - Kifagi, Chamseddine
AU - Ristic, Marko
AU - Akl, Dana
AU - Hallal, Rawan
AU - Carusi, Aude
AU - Gabellier, Ludovic
AU - de Toledo, Marion
AU - Sigurdsson, Jon-Otti
AU - Kaoma, Tony
AU - Andrieu-Soler, Charlotte
AU - Forné, Thierry
AU - Soler, Eric
AU - Hicheri, Yosr
AU - Gueret, Elise
AU - Vallar, Laurent
AU - Olsen, Jesper V.
AU - Cartron, Guillaume
AU - Piechaczyk, Marc
AU - Bossis, Guillaume
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2023
Y1 - 2023
N2 - Genotoxicants have been used for decades as front-line therapies against cancer on the basis of their DNA-damaging actions. However, some of their non-DNA-damaging effects are also instrumental for killing dividing cells. We report here that the anthracycline Daunorubicin (DNR), one of the main drugs used to treat Acute Myeloid Leukemia (AML), induces rapid (3 h) and broad transcriptional changes in AML cells. The regulated genes are particularly enriched in genes controlling cell proliferation and death, as well as inflammation and immunity. These transcriptional changes are preceded by DNR-dependent deSUMOylation of chromatin proteins, in particular at active promoters and enhancers. Surprisingly, inhibition of SUMOylation with ML-792 (SUMO E1 inhibitor), dampens DNR-induced transcriptional reprogramming. Quantitative proteomics shows that the proteins deSUMOylated in response to DNR are mostly transcription factors, transcriptional co-regulators and chromatin organizers. Among them, the CCCTC-binding factor CTCF is highly enriched at SUMO-binding sites found in cis-regulatory regions. This is notably the case at the promoter of the DNR-induced NFKB2 gene. DNR leads to a reconfiguration of chromatin loops engaging CTCF- and SUMO-bound NFKB2 promoter with a distal cis-regulatory region and inhibition of SUMOylation with ML-792 prevents these changes.
AB - Genotoxicants have been used for decades as front-line therapies against cancer on the basis of their DNA-damaging actions. However, some of their non-DNA-damaging effects are also instrumental for killing dividing cells. We report here that the anthracycline Daunorubicin (DNR), one of the main drugs used to treat Acute Myeloid Leukemia (AML), induces rapid (3 h) and broad transcriptional changes in AML cells. The regulated genes are particularly enriched in genes controlling cell proliferation and death, as well as inflammation and immunity. These transcriptional changes are preceded by DNR-dependent deSUMOylation of chromatin proteins, in particular at active promoters and enhancers. Surprisingly, inhibition of SUMOylation with ML-792 (SUMO E1 inhibitor), dampens DNR-induced transcriptional reprogramming. Quantitative proteomics shows that the proteins deSUMOylated in response to DNR are mostly transcription factors, transcriptional co-regulators and chromatin organizers. Among them, the CCCTC-binding factor CTCF is highly enriched at SUMO-binding sites found in cis-regulatory regions. This is notably the case at the promoter of the DNR-induced NFKB2 gene. DNR leads to a reconfiguration of chromatin loops engaging CTCF- and SUMO-bound NFKB2 promoter with a distal cis-regulatory region and inhibition of SUMOylation with ML-792 prevents these changes.
U2 - 10.1093/nar/gkad581
DO - 10.1093/nar/gkad581
M3 - Journal article
C2 - 37462077
VL - 51
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 16
ER -
ID: 361389321