Mutations in BCOR, a Co-Repressor of CRX/OTX2, Are Associated With Early-Onset Retinal Degeneration

Authors

Maéva Langouët
Christine Jolicoeur
Awais Javed
Pierre Mattar
Micah D Gearhart
Stephen P Daiger
Mette Bertelsen
Lisbeth Tranebjærg
Nanna D Rendtorff
Karen Grønskov
Catherine Jespersgaard
Rui Chen
Zixi Sun
Hui Li
Najmeh Alirezaie
Jacek Majewski
Vivian J Bardwell
Ruifang Sui
Robert K Koenekoop
Michel Cayouette

Publication Date

9-9-2022

Journal

Science Advances

Abstract

Many transcription factors regulating the production, survival, and function of photoreceptor cells have been identified, but little is known about transcriptional co-regulators in retinal health and disease. Here, we show that BCL6 co-repressor (BCOR), a Polycomb repressive complex 1 factor mutated in various cancers, is involved in photoreceptor degenerative diseases. Using proteomics and transcription assays, we report that BCOR interacts with the transcription factors CRX and OTX2 and reduces their ability to activate the promoters of photoreceptor-specific genes. CUT&RUN sequencing further shows that BCOR shares genome-wide binding profiles with CRX/OTX2, consistent with a general co-repression activity. We also identify missense mutations in human

Comments

Supplementary Materials

PMID: 36070393