PRC1 Sustains the Memory of Neuronal Fate Independent of PRC2 Function

Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early developmental patterning programs by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We unexpectedly found that PRC2 is dispensable to preserve the Hox transcription factor-dependent positional identity of spinal motor neurons (MNs), while PRC1 is essential for the specification of segmentally-restricted subtypes. Mutation of the core PRC1 component Ring1 leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox genes, while general features of MNs are maintained. Loss of MN subtype-specific fates in Ring1 mutants is due to the suppression of Hox networks by derepressed caudal Hox genes. These results indicate that PRC1 can function independently of de novo PRC2-dependent methylation to maintain chromatin topology and transcriptional identity at the time of differentiation. RNAseq and ATACseq of brachial thoracic and lumbar motor neurons in Ring1 mutants. RNAseq of ESC-derived motor neurons expressing Hoxc13.