Abstract
Epigenetic modifiers and transcription factors contribute to developmentally programmed gene expression. Here, we establish a functional link between epigenetic regulation by Polycomb group (PcG) proteins and transcriptional regulation by C/ebp that orchestrates the correct expression of Bombyx mori asparagine synthetase (BmASNS), a gene involved in the biosynthesis of asparagine. We show that the cis-regulatory elements of YY1-binding motifs and the CpG island present on the BmASNS promoter are required for the recruitment of PcG proteins and the subsequent deposition of the epigenetic repression mark H3K27me3. RNAi-mediated knockdown of PcG genes leads to derepression of the BmASNS gene via the recruitment of activators, including BmC/ebp, to the promoter. Intriguingly, we find that PcG proteins and BmC/ebp can dynamically modulate the transcriptional output of the BmASNS target in a cell cycle-dependent manner. It will be essential to suppress BmASNS expression by PcG proteins at the G2/M phase of the cell cycle in the presence of BmC/ebp activator. Thus, our results provide a novel insight into the molecular mechanism underlying the recruitment and regulation of the PcG system at a discrete gene locus in Bombyx mori.
Highlights
Polycomb group (PcG) proteins are conserved transcriptional repressors involved in regulating body formation during embryonic development [1], and have been characterized as chromatin modifiers required for the epigenetic regulation of numerous cellular processes, including cell cycle control, tumorigenesis, X-inactivation, cell fate decisions and differentiation [2,3,4,5,6].PcG proteins function via three key multiprotein complexes: Polycomb repressive complex 1 (PRC1), Polycomb repressive complex 2 (PRC2), and Pleiohomeotic repressive complex (PhoRC) [7,8,9]
Our results demonstrated that the Bombyx asparagine synthetase (ASNS) (BmASNS) gene is regulated by PcG-mediated repression and BmC/ebpmediated activation in a cell cycle-dependent manner
We noted that the further loss of expression of the Bombyx mori asparagine synthetase (BmASNS) gene mediated by RNA interference (RNAi) under the condition of amino acid starvation significantly decreased the cell growth, indicating an important role of BmAsns in cell proliferation
Summary
Polycomb group (PcG) proteins are conserved transcriptional repressors involved in regulating body formation during embryonic development [1], and have been characterized as chromatin modifiers required for the epigenetic regulation of numerous cellular processes, including cell cycle control, tumorigenesis, X-inactivation, cell fate decisions and differentiation [2,3,4,5,6].PcG proteins function via three key multiprotein complexes: Polycomb repressive complex 1 (PRC1), Polycomb repressive complex 2 (PRC2), and Pleiohomeotic repressive complex (PhoRC) [7,8,9]. The PRC1 complex, which includes Polycomb (Pc), Polyhomeotic (Ph), Sex combs extra (Sce), and Posterior sex combs (Psc) in Drosophila or their counterparts in mammals, is involved in recognizing the chromatin marked with tri-methylated histone H3 on lysine 27 (H3K27me3) [8]. PRC2 complex-mediated establishment of H3K27me is orchestrated by the recognition of Pleiohomeotic (Pho, a DNA-binding protein in the PhoRC complex) on specific DNA sequences called Polycomb responsive elements (PREs) in target genes [9], and by subsequent recruitment of other PcG components to the PREs region. Several studies have revealed that long non-coding (lnc) RNAs, short RNAs, or even CpG islands in target genes regulate the recruitment of PcG complexes in mammals [12,13,14,15]. There is insufficient evidence that an YY1-binding sequence is required for the recruitment of PcG complexes in mammals
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