TY - JOUR
T1 - Mutations in BCOR, a co-repressor of CRX/OTX2, are associated with early-onset retinal degeneration
AU - Langouët, Maéva
AU - Jolicoeur, Christine
AU - Javed, Awais
AU - Mattar, Pierre
AU - Gearhart, Micah D.
AU - Daiger, Stephen P.
AU - Bertelsen, Mette
AU - Tranebjærg, Lisbeth
AU - Rendtorff, Nanna D.
AU - Grønskov, Karen
AU - Jespersgaard, Catherine
AU - Chen, Rui
AU - Sun, Zixi
AU - Li, Hui
AU - Alirezaie, Najmeh
AU - Majewski, Jacek
AU - Bardwell, Vivian J.
AU - Sui, Ruifang
AU - Koenekoop, Robert K.
AU - Cayouette, Michel
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.abh2868
DO - 10.1126/sciadv.abh2868
M3 - Journal article
C2 - 36070393
AN - SCOPUS:85137421868
VL - 8
SP - eabh2868
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 36
ER -