Loss of PRC1 induces higher-order opening of Hox loci independently of transcription during Drosophila embryogenesis

Thierry Cheutin (1) , Giacomo Cavalli (1)

1 IGH - Institut de génétique humaine

Polycomb-group proteins are conserved chromatin factors that maintain the silencing of key developmental genes, notably the Hox gene clusters, outside of their expression domains. Depletion of Polycomb repressive complex 1 (PRC1) proteins typically results in chromatin unfolding, as well as ectopic transcription. To disentangle these two phenomena, here we analyze the temporal function of two PRC1 proteins, Polyhomeotic (Ph) and Polycomb (Pc), on Hox gene clusters during Drosophila embryogenesis. We show that the absence of Ph or Pc affects the higher-order chromatin folding of Hox clusters prior to ectopic Hox gene transcription, demonstrating that PRC1 primary function during early embryogenesis is to compact its target chromatin. Moreover, the differential effects of Ph and Pc on Hox cluster folding match the differences in ectopic Hox gene expression observed in these two mutants. Our data suggest that PRC1 maintains gene silencing by folding chromatin domains and impose architectural layer to gene regulation.

Domaines: Sciences du Vivant [q-bio]; Génétique

Thierry Cheutin, Giacomo Cavalli. Loss of PRC1 induces higher-order opening of Hox loci independently of transcription during Drosophila embryogenesis. Nature Communications, 2018, 9 (1), pp.3898. ⟨10.1038/s41467-018-05945-4⟩. ⟨hal-01887463⟩