Mutations in BCOR, a co-repressor of CRX/OTX2, are associated with early-onset retinal degeneration

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

Research output: Contribution to journalArticlepeer-review


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 BCOR in five families that have no evidence of cancer but present severe early-onset X-linked retinal degeneration. Last, we show that the human BCOR mutants cause degeneration when expressed in the mouse retina and have enhanced repressive activity on OTX2. These results uncover a role for BCOR in photoreceptors in both health and disease.

Original languageEnglish (US)
Article numbereabh2868
JournalScience Advances
Issue number36
StatePublished - Sep 9 2022

Bibliographical note

Funding Information:
This work was funded by grants from the NIH (R01HD084459 to V.J.B. and R01-030499-01 to R.K.K.), the Canadian Institutes of Health Research (to R.K.K. and M.C.; FDN-159936), Fighting Blindness Canada (to R.K.K. and M.C.), FRQS Vision Health Research Network (to R.K.K.), and the Montreal Children's Hospital Foundation (to R.K.K.). Additional funding: The National Science Foundation of China grant (81873687) and CAMS innovation fund for medical sciences (CIFMS 2016-12 M-1-002) to R.S. This work was also supported by grants from the National Eye Institute (R01EY022356 and R01EY018571 to R.C.), the NIH (EY007142), the Foundation Fighting Blindness, and the William Stamps Farish Fund (to S.P.D.). L.T. received funding from The Research Foundation at Mo Gård. M.C. is an Emeritus Scholar from the FRQS and holds the Gaëtane and Roland Pillenière Chair in Retina Biology from the IRCM Foundation

Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PubMed: MeSH publication types

  • Journal Article


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