NURD-complex genes antagonise Ras-induced vulval development in Caenorhabditis elegans.

Chromatin-modifying complexes are important for transcriptional control, but their roles in the regulation of development are poorly understood. Here, we show that components of the nucleosome remodelling and histone deacetylase (NURD) complex [1] [2] [3] [4] [5] antagonise vulval development, which is induced by the Ras signal transduction pathway. In three of the six equivalent vulval precursor cells, the Ras pathway is active, leading to the production of vulval fates [6]; in the remaining three, the Ras pathway is inhibited and vulval fates repressed. Inhibition of Ras signaling occurs in part through the action of the synthetic multivulval (synMuv) genes, which comprise two functionally redundant pathways (synMuvA and synMuvB) [7]. We found that five Caenorhabditis elegans members of the NURD chromatin remodelling complex inhibit vulval development through both the synMuvA and synMuvB pathways (hda-1, rba-1, lin-53, chd-3 and chd-4); a further two members, the MTA1-related genes egr-1 and egl-27, act only in the synMuvA pathway. We propose that the synMuvA and synMuvB pathways function redundantly to recruit or activate a core NURD complex, which then represses vulval developmental target genes by local histone deacetylation. These results emphasise the importance of chromatin regulation in developmental decisions. Furthermore, inhibition of Ras signaling suggests a possible link between NURD function and cancer.

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