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Sustainable Imine Production Using Alkanes as Substrates via a Plasma-Microdroplet Approach
Targeting Msx2 as a brake in the fusion fate of osteoclasts and an anabolic therapy in pre-clinical models of osteoporosis
AI-derived CT biomarker score for robust COVID-19 mortality prediction across multiple waves and regions using machine learning
The real problems with America's health
Enantioselective Total Synthesis of Bipolarolides A and B
Author Correction: Enantioselective aza-electrophilic dearomatization of naphthalene derivatives
Coal-forming sedimentary model and its control on vertical reservoir heterogeneity of the upper carboniferous Benxi formation in Ordos basin, China
Construction of a <i>De Novo</i> Nucleotide Biosynthesis Pathway in Artificial Cells for RNA Transcription
IRX3 controls a SUMOylation-dependent differentiation switch in adipocyte precursor cells
Abstract IRX3 is linked to predisposition to obesity through the FTO locus and is upregulated during early adipogenesis in risk-allele carriers, shifting adipocyte fate toward fat storage. However, how this elevated IRX3 expression influences later developmental stages remains unclear. Here we show that IRX3 regulates adipocyte fate by modulating epigenetic reprogramming. ChIP-sequencing in preadipocytes identifies over 300 IRX3 binding sites, predominantly at promoters of genes involved in SUMOylation and chromatin remodeling. IRX3 knockout alters expression of SUMO pathway genes, increases global SUMOylation, and inhibits PPARγ activity and adipogenesis. Pharmacological SUMOylation inhibition rescues these effects. IRX3 KO also reduces SUMO occupancy at Wnt-related genes, enhancing Wnt signaling and promoting osteogenic fate in 3D cultures. This fate switch is partially reversible by SUMOylation inhibition. We identify IRX3 as a key transcriptional regulator of epigenetic programs, acting upstream of SUMOylation to maintain mesenchymal identity and support adipogenesis while suppressing osteogenesis in mouse embryonic fibroblasts.
Saltations of cis-regulatory modules in Canidae and Hominidae
Abstract Dogs, which were segregated from wolves about thirty thousand years ago, show unique human-similar social-cognitive abilities. However, the genomic basis accounting for the phenotypic saltation between dog and wolf remains unclear. We performed a comparative analysis of genome-wide cis-regulatory element frequencies (CREF) for five canids: dog, dingo, red fox, dhole, and wolf, along with four hominids. For each species, genome-wide CREFs are organized into a matrix. The species-specific CREF matrix is stratified into multiple dual eigen-modules through robust singular value decomposition. Cross-species comparisons of dual eigen-modules demonstrated that the top three eigen-modules are highly conserved while the fourth and fifth ones underwent a saltation in dogs. The red fox is closest to the degenerate point characterizing the onset of saltation. Gene enrichment analysis and motif analysis revealed that myelination, long-term memory, and cochlear development are significantly enhanced at level four in both humans and dogs, but not in wolves. Cross-family comparisons revealed a more similar cognition-memory module between humans and dogs than between humans and chimpanzees. Not only the presence of cis-elements but also their frequencies are crucial for deciphering the regulatory saltations that characterize a striking convergent evolution of dogs and humans in proximal regulatory sequences.