Mutations in BCOR, a co-repressor of CRX/OTX2, are associated with early-onset retinal degeneration.
Mutations in BCOR, a co-repressor of CRX/OTX2, are associated with early-onset retinal degeneration.
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DOI：
10.1126/sciadv.abh2868
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发表时间：
2022-09-09
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
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作者：
许多调节光感受器细胞的产生、存活和功能的转录因子已经被发现，但对视网膜健康和疾病中的转录协同调节因子知之甚少。在这里，我们证明了BCL6共抑制因子(BCOR)，一种在多种癌症中突变的多梳抑制复合体1因子，参与了光感受器退行性疾病。利用蛋白质组学和转录分析，我们报道了BCOR与转录因子CRX和OTX2相互作用，并降低了它们激活光感受器特异基因启动子的能力。切割和运行测序进一步表明，BCOR与CRX/OTX2共享全基因组结合谱，与一般的共抑制活性一致。我们还在五个没有癌症证据但出现严重的早发性X-连锁视网膜变性的家庭中发现了人类BCOR的错义突变。最后，我们发现人类BCOR突变体在小鼠视网膜中表达时会导致退化，并增强了对OTX2的抑制活性。这些结果揭示了BCOR在光感受器中对健康和疾病的作用。BCOR调节OTX2和CRX的转录活性，并控制小鼠和人类的光感受器存活。
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. BCOR regulates OTX2 and CRX transcriptional activity and controls photoreceptor survival in mice and humans.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
在发育，重编程和肿瘤发生过程中，视网膜的动态表观遗传景观。
影响因子：
16.2
作者：
Aldiri I;Xu B;Wang L;Chen X;Hiler D;Griffiths L;Valentine M;Shirinifard A;Thiagarajan S;Sablauer A;Barabas ME;Zhang J;Johnson D;Frase S;Zhou X;Easton J;Zhang J;Mardis ER;Wilson RK;Downing JR;Dyer MA;St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project
通讯作者：
St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project
影响因子：
--
作者：
Fossat, Nicolas;Le Greneur, Coralie;Beby, Francis;Vincent, Stephane;Godement, Pierre;Chatelain, Gilles;Lamonerie, Thomas
通讯作者：
Lamonerie, Thomas
影响因子：
2.7
作者：
Hamline, Michelle Y.;Corcoran, Connie M.;Wamstad, Joseph A.;Miletich, Isabelle;Feng, Jifan;Lohr, Jamie L.;Hemberger, Myriam;Sharpe, Paul T.;Gearhart, Micah D.;Bardwell, Vivian J.
通讯作者：
Bardwell, Vivian J.