Project description:Skeletal muscle is a heterogeneous tissue. To study the myo-specific epigenetic landscape in the slow soleus and fast extensor digitorum longus (EDL) muscle, myonuclei were purified with PCM1 -an endogenous mark specific for mature myonuclei. Chromatin immunoprecipitation sequencing (ChIP-Seq) was performed using antibodies against the histone marks H3K4me3 and H3K27ac. Comparison of the differently enriched areas between the two muscles shows that the epigenetic landscape reflects the functional properties of the muscles, each with a distinct regulatory program involving distal regulatory enhancers.
Project description:The epigenomic regulation is a part of Gene Regulatory Network (GRN). During we study the reprogramming of GRN adaptive to atrophic stimulation in skeletal muscle, we performed Histone 3 lysine 27 (H3K27) acetylation (H3K27ac) ChIP-seq assay using mouse skeletal muscle with or without denervation. This dataset combining with our snATAC datasets enable us to infer the candidate enhancer that could regulate muscle protein metabolism and energy metabolism during atrophy.
Project description:To study the tissue-specific evolution of regulatory elements in the mammalian lineage, we created a comprehensive map of promoters and enhancers in 4 tissues of 10 mammalian species. To map in-vivo promoters and enhancers, we performed ChIP-seq experiments for H3K4me3, H3K27ac and H3K4me1 in adult liver, muscle, brain and testis of all 10 species. The species included in the study are: macaque, marmoset, mouse, rat, rabbit, pig, dog, cat, horse and opossum. To correlate regulatory evolution to expression, we also performed RNA-seq experiments in all tissues and species submitted separately to ArrayExpress.
Project description:A variety of epigenetic alterations impairs functions of cells and tissues during aging, but it is not known if epigenetic alterations are associated with aging muscle. Here, we examined the changes of a panel of histone marks and found H3K27ac (an active enhancer mark) is markedly increased during aging in human skeletal muscle tissues. Our integrated analysis showed that enhancer activation during muscle aging is associated with the up-regulation of extracelluar matrix (ECM) genes, which may result in stiffness of the niche environment of satellite cells (SCs). An age-related fibrogenic conversion of geriatric SCs was observed through differential gene expression analysis. In mice, treatment of aging muscles with JQ1, an inhibitor of enhancer activation reverted the ECM up-regulation and fibrogenic conversion of SCs, suggesting that ECM increase in aging muscle is indeed a result of enhancer activation. The study here not only uncovered a novel aspect of muscle aging that is associated with enhancer remodeling but also highlighted JQ1 as a potential treatment approach for restoring SC function in aging muscle.
Project description:Considered as fundamental epigenetic regulators controlling many key cellular processes, histone modifications are a well-conserved and widely studied class of epigenetic modifications. Genome-wide studies have identified enhancers as DNA sequences that bind to H3K4me1 and H3K27ac and promoters as DNA sequences that bind to H3K4me3. To explore how the Twist1 complex (Twist1/YY1/p300) regulates miR-9 expression, we performed ChIP-seq in PLC-PRF-5 cells, providing a panorama of p300, H3K4me3, H3K4me1, and H3K27ac.
Project description:Chromatin immunoprecipitation sequencing of H3K4me2, H3K27ac as well as, ATACseq and RNA-seq reveals regulatory landscapes across different muscle groups, as well as in response to chronic exercise or muscle PGC1a overexpression. This work defines the unique enhancer repetoire of skeletal muscle in vivo and reveals that highly divergent exercise-induced or PGC1a-driven epigenomic programs direct partially convergent transcriptional networks.