Pharmacologic management of postoperative sleep disturbance in breast cancer.

Multiprotein complexes are essential building blocks of life, from viruses to humans. They ensure the faithful structural–functional harmony of enzymes, phase-separated condensates, sub-cellular organelles, cells, tissues, organs, and entire organisms. Remarkable progress has been achieved in identifying and characterizing thousands of endogenous multiprotein complexes (EMCs) in hundreds of species, including humans (; ; ; ; ; ). However, it remains unknown whether common mechanisms of EMC biogenesis exist that guide the initiation of the multistep molecular assembly of highly diverse arrays of EMC components. Therefore, understanding the fundamental principles governing the dynamics of EMC assembly remains one of the most significant challenges in contemporary biological and biomedical sciences. DNA sequences derived from transposable elements (TEs) constitute approximately 50% of the human genome, contributing to a multitude of structural features and regulatory functions at different levels of genomic organization (; ; ; ; ). During evolution, concurrently with TE colonization of primate genomes, a highly sophisticated defense system co-evolved. This system was designed to restrict uncontrolled TE expansion and diminish potentially deleterious effects of TE insertions on genome integrity, while also providing TE family sequence-specific co-option mechanisms that integrate TE-derived sequences into cell type- and tissue-specific genomic regulatory networks (; ; ). While the potentially destructive effects of TEs on genome integrity represent their ubiquitous biological feature, defined by the very nature of transpositionally competent TEs, it remains less clear whether TE-derived DNA sequences may possess similarly ubiquitous non-deleterious functions, perhaps contributing to the evolutionary fitness of the host. TE-derived sequences are often integrated into species’ genomic regulatory networks. In mammalian genomes, TE-derived sequences have rewired the core regulatory circuitry of embryonic stem cells (). They are intrinsically activated in human preimplantation embryos () by operating as long-range enhancers () and providing transcription factor binding sites (TFBS) for TP53 (), STAT1 (), and CTCF (). This includes a set of transcription factors (TFs) defined as master pluripotency regulators (; ), with candidate human-specific TFBS for POU5F1 (OCT4), NANOG, SOX2, and CTCF (, ; ). Overall, chromatin immunoprecipitation and sequencing (ChIP-seq) experiments have demonstrated that TE-derived loci harbor thousands of TFBS, presumably exerting global regulatory effects on gene expression in various pathophysiological conditions. However, the distribution of TFBS is non-uniform and highly variable within specific TE subfamilies that evolutionarily emerged from identical or highly similar sequences. TE sequence-dependent distribution of TFBS is likely influenced by genetic drift and other mutational processes, as well as cell type-specific epigenetic contexts affecting chromatin states of genomic regions harboring TE insertions.