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Background While the role of Polycomb group protein-mediated “cell memory” is well established in developmental contexts, little is known about their role in adult tissues and in particular in post-mitotic cells. Emerging evidence assigns a pivotal role in cell plasticity and adaptation. PRC2-Ezh1α/β signaling pathway from cytoplasm to chromatin protects skeletal muscle cells from oxidative stress. However, detailed mechanisms controlling degradation of cytoplasmic Ezh1β and assembly of canonical PRC2-Ezh1α repressive complex remain to be clarified. Results Here, we report NEDD4 ubiquitin E3 ligase, as key regulator of Ezh1β. In addition, we report that ubiquitination and degradation of Ezh1β is controlled by another layer of regulation, that is, one specific phosphorylation of serine 560 located at Ezh1β-specific C terminal. Finally, we demonstrate that also Ezh1α needs to be stabilized under stress condition and this stabilization process requires decreased association pattern between another E3 ubiquitin ligase HUWE1. Conclusions Together, these results shed light on key components that regulate PRC2-Ezh1α/β pathway to direct modulation of epigenome plasticity and transcriptional output in skeletal muscle cells.

Additional file 6: Table S2. Primary antibodies information used in this study.

Additional file 1: Fig. S1. Construction of stable C2C12 cell line constitutively expressing Ezh1β. Fig. S2. Increased poly-ubiquitination status of Ezh1β under oxidative stress condition. Fig. S3. Degradation of Ezh1β-FH is dependent on 26S proteasome system. Fig. S4. HUWE1, NEDD4 and FBXW8 knock-down stable cell line construction. Fig. S5. Minor effect of HUWE1 and FBXW8 in regulating stability of Ezh1β under oxidative stress condition. Fig. S6. Dynamic interaction between Ezh1β and NEDD4 under normal and oxidative stress conditions. Fig. S7. Construction of Ezh1α-FH stable cell line. Fig. S8. CHX chasing assay of Ezh1α-FH under normal condition.

Additional file 5: Table S1. Oligos sequence information used in this study.

Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneously. We present a temporal and spatial atlas of circadian metabolism in the context of systemic energy balance and under chronic nutrient stress (high-fat diet [HFD]). Comparative analysis reveals how the repertoires of tissue metabolism are linked and gated to specific temporal windows and how this highly specialized communication and coherence among tissue clocks is rewired by nutrient challenge. Overall, we illustrate how dynamic metabolic relationships can be reconstructed across time and space and how integration of circadian metabolomics data from multiple tissues can improve our understanding of health and disease.