Trends in Genetics最新文献

Linker histone H1 is a fundamental chromatin component, essential for higher-order chromatin compaction and transcriptional regulation. Chromatin regulator associated with M phase protein 1 (CRAMP1) was recently identified as a highly conserved factor that promotes the transcription of both replication-dependent and replication-independent H1 variants. This review synthesizes evidence that CRAMP1-mediated H1 production is critical for development via epigenetic regulation. We further summarize the multifaceted roles of H1 in maintaining genome integrity by facilitating heterochromatin formation and by serving as a key suppressor of transposable elements from Drosophila to mammals. Finally, we discuss how post-translational modifications on H1 dynamically regulate its function in chromatin dynamics and the DNA damage response. Collectively, this overview positions H1 and its master regulator CRAMP1 as important players in chromatin organization, with emerging roles in development, genome defense, and disease.

Transcription is not only an essential cellular process but also a major source of endogenous DNA strand breaks. Many cancers exhibit transcriptional addiction and rely on dysregulated and excessive transcription to maintain the malignant state. We review recent advances in transcription-associated DNA breaks and their role as an essential player in endogenous fragility. We highlight the contrast between replication-dependent transcriptional breaks (e.g., transcription-replication conflicts) and replication-independent transcriptional breaks (resulting from transcription itself). We outline two types of transcriptional double-strand breaks (DSBs): promoter-associated breaks that are linked to gene activation, and gene-body breaks that occur stochastically from transcription byproducts. We discuss how supercoiling, R-loops, and enhancer-promoter looping at super-enhancer (SE)-regulated loci can increase DNA fragility and thereby create a distinct Achilles' heel, and propose that targeting the coupling between SE-driven transcription and DNA repair could offer new therapeutic strategies for cancer.

Twenty-five years after the histone code hypothesis proposed that combinations of histone post-translational modifications (PTMs) direct gene regulation, fundamental questions remain unresolved. Here, I outline a call for a multi-laboratory initiative, termed HistENCODE, to systematically decipher functional relationships between histone PTMs via direct mutagenesis of histone N-terminal tail residues.

Z-DNA is a left-handed alternative DNA structure that forms at alternating purine-pyrimidine repeats, which are abundant in genomes. It is intrinsically unstable under physiological conditions; however, it can be stabilized by negative supercoiling and specific Z-DNA binding proteins. These stabilizing factors have prompted renewed interest in the biological significance of Z-DNA within the genome. Emerging evidence suggests that Z-DNA plays critical roles in various cellular processes, including transcriptional regulation, genome instability, chromatin remodeling, and the development of human diseases. This review summarizes existing methodologies for local and global identification of Z-DNA, its genomic and epigenetic features, the factors influencing its formation and stability, its biological implications, and future directions to advance our understanding of Z-DNA biology and its potential applications.

Gene activity is intricately shaped by its chromatin environment. Deciphering the chromatin landscape is essential for understanding the complex regulatory networks governing gene function. The newly re-recognized DNA N⁶-methyladenine (6mA) is relatively scarce in multicellular eukaryotes, which has facilitated the development of innovative chromatin profiling approaches employing sequence-independent 6mA methyltransferases (MTases) to introduce exogenous 6mA. In this review, we summarize recent advances in leveraging exogenous 6mA deposition and long-read sequencing in three major applications: chromatin landscape profiling, protein-DNA interaction mapping, and targeted epigenetic editing. For each, we outline representative workflows, highlight technical advantages, and discuss current challenges and prospects for optimization. Together, this review underscores the emerging power of exogenous 6mA as a versatile tool for decoding chromatin architecture and gene regulation.

Beyond their degradative role, lysosomes help prepare Caenorhabditis elegans offspring for stress. In a recent study, Zhang et al. show that lysosomal activation induces somatic histone H3.3 production, which moves to the germline and is methylated at K79 to transmit longevity. Thus, this work establishes lysosomes as a conduit linking metabolism, chromatin, and epigenetic inheritance.

Researchers often assume genomic results are too complex for lay communities, but heredity concepts are widely understood. Effective return of results depends on cultural context, clear communication, and collaboration with communities. Tailored, respectful approaches foster trust and ensure research benefits are meaningful, accessible, and empowering.

Mutational robustness, the ensemble of mechanisms that allow organisms to maintain a stable phenotype despite genetic mutations, affects adaptive evolution in several ways. Many models have attempted to explain how mutational robustness might evolve and shape adaptation, but the variety of approaches and assumptions complicates a clear synthesis. Here, we categorize and critically discuss the main approaches for modeling the evolutionary causes and consequences of mutational robustness. We discuss how robustness can emerge from aspects of biological organization (e.g., modularity, critical dynamics) and selection (e.g., stabilizing selection) and how robustness can both enhance and constrain evolvability [e.g., through cryptic genetic variation (CGV)]. We conclude by discussing challenges related to model complexity and computational cost and outline the foremost outstanding questions.

The power of short-read DNA sequencing in biodiversity research and evolutionary genomics is rapidly growing due to advances in technology and bioinformatics. Short-read sequencing offers powerful solutions for taxonomic identification, biomass estimation, and phylogenetic reconstruction. Moreover, short-read data enable robust estimation of genome size and repeat content, offering valuable insights into genome evolution. Though growing in popularity, long-read genome assemblies are often not feasible with material from museum collections or raw biodiversity samples. With the growing demand for DNA-based approaches in biodiversity research, short-read genomics provides an easily generated universal data source spanning all levels from individual genomes to ecosystems, and including all species on Earth, to achieve the objectives of the Global Biodiversity Framework (GBF) for the preservation of biodiversity.

Recent studies have reported that catalytically dead histone-modifying enzymes can rescue the function of their null alleles. Histone 'replacement' experiments have similarly found a lack of phenotypes for some modifications. Do these findings foretell a paradigm shift for the histone code hypothesis? Here, we discuss these results through the lens of ecology, evolution, and development ('eco-evo-devo') to provide context. We then highlight recent 'top-down' approaches, which start from environmentally influenced phenotypes and then attempt to identify causal mechanisms; placing function before molecule. Using this strategy, recent work in invertebrates has found key roles for histone acetylation and small RNAs in developmental plasticity. The synthesis of traditional 'bottom-up' with new 'top-down' approaches can resolve which molecules are epiphenomenal and which are truly epigenetic.