| http://purl.uniprot.org/citations/33482083 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33482083 | http://www.w3.org/2000/01/rdf-schema#comment | "The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a GGGGCC repeat expansion in the C9orf72 gene. We developed a platform to interrogate the chromatin accessibility landscape and transcriptional program within neurons during degeneration. We provide evidence that neurons expressing the dipeptide repeat protein poly(proline-arginine), translated from the C9orf72 repeat expansion, activate a highly specific transcriptional program, exemplified by a single transcription factor, p53. Ablating p53 in mice completely rescued neurons from degeneration and markedly increased survival in a C9orf72 mouse model. p53 reduction also rescued axonal degeneration caused by poly(glycine-arginine), increased survival of C9orf72 ALS/FTD-patient-induced pluripotent stem cell (iPSC)-derived motor neurons, and mitigated neurodegeneration in a C9orf72 fly model. We show that p53 activates a downstream transcriptional program, including Puma, which drives neurodegeneration. These data demonstrate a neurodegenerative mechanism dynamically regulated through transcription-factor-binding events and provide a framework to apply chromatin accessibility and transcription program profiles to neurodegeneration."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cell.2020.12.025"xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Han K."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Zhang Y.J."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Santana M."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Tessier-Lavigne M."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Geschwind D.H."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Bassik M.C."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Sinnott-Armstrong N."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Ramaswami G."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Gitler A.D."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Petrucelli L."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Gao F.B."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Linares G.R."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Ruan K."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Attardi L.D."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Greenleaf W.J."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Simon D.J."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Lloyd T.E."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Ichida J.K."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Couthouis J."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Yokoyama J.S."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Shipony Z."xsd:string |
| http://purl.uniprot.org/citations/33482083 | http://purl.uniprot.org/core/author | "Blum J.A."xsd:string |