GEMC1 and MCIDAS Interactions with SWI/SNF Complexes Regulate the Multiciliated Cell-Specific Transcriptional Program

Autor: Haotian Zhao, Moe R. Mahjoub, Gabriel Gil-Gómez, Tao Cheng, Sudipto Roy, Michael Lewis, Gabrielle Piergiovanni, Philip A. Knobel, Sandra Peiró, Jessica Querol, Camille Stephan-Otto Attolini, Brian Raught, Berta Terré, Vincenzo Costanzo, Travis H. Stracker, Hao Lu, Isabel Garcia-Cao, Etienne Coyaud
Rok vydání: 2020
Předmět:
Zdroj: SSRN Electronic Journal.
ISSN: 1556-5068
Popis: 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 and MCIDAS with the BRD9 containing ncBAF complex. Inhibition of BRD9 impaired MCIDAS-mediated activation of several target genes and compromised MCC differentiation. Our data suggest that the differential engagement of distinct SWI/SNF subcomplexes by GEMC1 and MCIDAS is required for MCC-specific transcriptional regulation.
Databáze: OpenAIRE