GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Lewis, Michael
  • dc.contributor.author Gil Gómez, Gabriel
  • dc.contributor.author Stracker, Travis H.
  • dc.date.accessioned 2024-03-15T09:52:20Z
  • dc.date.available 2024-03-15T09:52:20Z
  • dc.date.issued 2023
  • dc.description.abstract Multiciliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiation of MCCs requires the sequential action of the Geminin family transcriptional activators, GEMC1 and MCIDAS, that both interact with E2F4/5-DP1. How these factors activate transcription and the extent to which they play redundant functions remains poorly understood. Here, we demonstrate that the transcriptional targets and proximal proteomes of GEMC1 and MCIDAS are highly similar. However, we identified distinct interactions with SWI/SNF subcomplexes; GEMC1 interacts primarily with the ARID1A containing BAF complex while MCIDAS interacts primarily with BRD9 containing ncBAF complexes. Treatment with a BRD9 inhibitor impaired MCIDAS-mediated activation of several target genes and compromised the MCC differentiation program in multiple cell based models. Our data suggest that the differential engagement of distinct SWI/SNF subcomplexes by GEMC1 and MCIDAS is required for MCC-specific transcriptional regulation and mediated by their distinct C-terminal domains.
  • dc.description.sponsorship ML and BT were funded by Severo Ochoa FPI fellowships from the Ministry of Science, Innovation and Universities (MCIU), PK by an Advanced Postdoc Mobility fellowship from the Swiss National Science Foundation and the Kurt and Senta Herrmann Foundation and I.G.C by an AECC fellowship. THS was funded by the MCIU (PGC2018-095616-B-I00/GINDATA) and by the NIH Intramural Research Program, National Cancer Institute, Center for Cancer Research. X.S. was supported by MINECO (PID2019-110198RB-I00) and the European Research Council (CONCERT, contract number 648201). IRB Barcelona is the recipient of institutional funding from FEDER and the Centres of Excellence Severo Ochoa award to IRB Barcelona from MINECO (Government of Spain). MRM was funded by the National Heart, Lung and Blood Institute of the NIH (R01-HL128370). VC was funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC), the European Research Council (ERC) grant 614541 and the GiovanniArmenise foundation career development award to VC. SR was funded by a Singapore National Medical Research Council (NMRC) Open Fund-Individual Research Grant (OFIRG19nov-0037). HZ was supported by National Cancer Institute (R01 CA220551).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Lewis M, Terré B, Knobel PA, Cheng T, Lu H, Attolini CS, et al. GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program. Cell Death Dis. 2023 Mar 17;14(3):201. DOI: 10.1038/s41419-023-05720-4
  • dc.identifier.doi http://dx.doi.org/10.1038/s41419-023-05720-4
  • dc.identifier.issn 2041-4889
  • dc.identifier.uri http://hdl.handle.net/10230/59432
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Cell Death Dis. 2023 Mar 17;14(3):201
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/648201
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-095616-B-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110198RB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/614541
  • dc.rights This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Proteïnes nuclears
  • dc.subject.other Regulació genètica
  • dc.subject.other Expressió gènica
  • dc.subject.other Diferenciació cel·lular
  • dc.title GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Hospital del Mar Research Institute)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)