GEMC1 and MCIDAS interactions with SWI/SNF ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program.
Author(s) :
Lewis, M. [Auteur]
Terré, B. [Auteur]
Knobel, P. A. [Auteur]
Cheng, T. [Auteur]
Lu, H. [Auteur]
Attolini, C. S. [Auteur]
Smak, J. [Auteur]
Coyaud, Etienne-Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Garcia-Cao, I. [Auteur]
Sharma, S. [Auteur]
Vineethakumari, C. [Auteur]
Querol, J. [Auteur]
Gil-Gómez, G. [Auteur]
Piergiovanni, G. [Auteur]
Costanzo, V. [Auteur]
Peiró, S. [Auteur]
Raught, B. [Auteur]
Zhao, H. [Auteur]
Salvatella, X. [Auteur]
Roy, S. [Auteur]
Mahjoub, M. R. [Auteur]
Stracker, T. H. [Auteur]
Terré, B. [Auteur]
Knobel, P. A. [Auteur]
Cheng, T. [Auteur]
Lu, H. [Auteur]
Attolini, C. S. [Auteur]
Smak, J. [Auteur]
Coyaud, Etienne-Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Garcia-Cao, I. [Auteur]
Sharma, S. [Auteur]
Vineethakumari, C. [Auteur]
Querol, J. [Auteur]
Gil-Gómez, G. [Auteur]
Piergiovanni, G. [Auteur]
Costanzo, V. [Auteur]
Peiró, S. [Auteur]
Raught, B. [Auteur]
Zhao, H. [Auteur]
Salvatella, X. [Auteur]
Roy, S. [Auteur]
Mahjoub, M. R. [Auteur]
Stracker, T. H. [Auteur]
Journal title :
Cell Death and Disease
Abbreviated title :
Cell Death Dis
Volume number :
14
Pages :
201
Publication date :
2023-03-19
ISSN :
2041-4889
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
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 ...
Show more >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.Show less >
Show more >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.Show less >
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2023-12-13T03:48:00Z
2024-01-26T12:30:27Z
2024-01-26T12:30:27Z
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