| First Author | Liu S | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 22 | Pages | 4663-4676.e8 |
| PubMed ID | 34637754 | Mgi Jnum | J:315705 |
| Mgi Id | MGI:6831142 | Doi | 10.1016/j.molcel.2021.09.020 |
| Citation | Liu S, et al. (2021) NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain. Mol Cell 81(22):4663-4676.e8 |
| abstractText | The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its HX repeat domain gives rise to misregulation of a subset of developmental genes and curtails motor neuron differentiation of mouse embryonic stem cells. The transcription factor nuclear respiratory factor 1 (NRF1) has a novel and integral role in this neurodevelopmental process, being required for ncPRC1.3 recruitment to chromatin. |
