Polycomb requires Tcp-1η chaperonin for maintaining gene silencing in Drosophila

Abstract In metazoans, heritable states of cell type specific gene expression patterns linked with specialization of various cell types constitute transcriptional cellular memory. Evolutionarily conserved Polycomb group (PcG) and trithorax group (trxG) proteins contribute to the transcriptional cellular memory by maintaining heritable patterns of repressed and active expression states, respectively. Although chromatin structure and modifications appear to play a fundamental role in maintenance of repression by PcG, the precise targeting mechanism and the specificity factors that bind PcG complexes to a defined region in chromosomes remain elusive. Here we report a serendipitous discovery that uncovers a direct molecular interaction between Polycomb (PC) and TCP-1 Ring Complex (TRiC) chaperonin subunit, Tcp-1η in Drosophila . Tcp-1η interacts with PC at chromatin to maintain repressed states of homeotic and non-homeotic targets of PcG, which supports a strong genetic interaction observed between Pc and Tcp-1η mutants. Depletion of Tcp-1η results in dissociation of PC from chromatin and redistribution of an abundant amount of PC in cytoplasm. We propose that Tcp-1η is an important modulator of PC, which helps PC recruitment at chromatin and compromising Tcp-1η can directly influence an evolutionary highly conserved epigenetic network that supervises the appropriate cellular identities during development and homoeostasis of an organism. Significance Statement Silencing of key developmental genes, e.g, Hox genes, by PcG is a hallmark of differential gene expression patterns associated with cell fate determination. Here we describe a previously unknown molecular and genetic interaction of Polycomb (PC) with Tcp-1η subunit of TRiC chaperonin complex in Drosophila . Compromising Tcp-1η function results in de-repression of PcG targets and a concomitant loss of PC from chromatin. Moreover, depletion of Tcp-1η leads to redistribution of PC in cytoplasm. Molecular interaction of PC with Tcp-1η highlights a novel factor which helps PC recruitment at chromatin. We propose that Tcp-1η chaperonin is one of the specificity factors and part of the targeting mechanism that binds PC to specific regions on chromosomes.