PRC1 sustains the integrity of neural fate in the absence of PRC2 function.

Abstract

Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early fate decisions 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 found that PRC1 is essential for the specification of segmentally restricted spinal motor neuron (MN) subtypes, while PRC2 activity is dispensable to maintain MN positional identities during terminal differentiation. Mutation of the core PRC1 component <i>Ring1</i> in mice leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including <i>Hox</i> transcription factors, while neuronal class-specific features are maintained. Loss of MN subtype identities in <i>Ring1</i> mutants is due to the suppression of Hox-dependent specification programs by derepressed <i>Hox13</i> paralogs (<i>Hoxa13</i>, <i>Hoxb13</i>, <i>Hoxc13</i>, <i>Hoxd13</i>). These results indicate that PRC1 can function in the absence of de novo PRC2-dependent histone methylation to maintain chromatin topology and postmitotic neuronal fate.