Biomedical subjects

Jian Yan

Publications and source records attributed to Jian Yan.

2 recordsLinked to original sources

PubMed2026

Decoding sequence recognition code of nucleic acid-binding proteins of human-infecting DNA viruses.

Human-infecting DNA viruses remain major health threats, yet the DNA-recognition mechanisms of their nucleic acid-binding proteins (NBPs) are poorly understood. Here, we systematically profiled 103 viral NBPs from human-infecting DNA viruses, with three NBPs from non-human-infecting DNA viruses as controls, using high-throughput screening. This analysis identified diverse DNA-binding motifs and specificity modules, including convergent recognition of a conserved CCACC motif across phylogenetically distant viruses. Notably, viral NBP binding-site distributions varied with genome size, and several NBPs from small-genome viruses showed enrichment on mitochondrial DNA. Functional assays further supported their mitochondrial association and effects on mitochondrial membrane potential. By integrating an ivTRT-based ssDNA-SELEX workflow, we further found that ssDNA viral NBPs recognize dimer-like and inverted-repeat sequences with potential to form stem-loop structures. Collectively, this study constructs a comprehensive viral NBP DNA-recognition atlas, offering a fundamental resource for elucidating viral genome recognition mechanisms, virus-mitochondria interactions, and developing future antiviral strategies.

Letter↗

PubMed2026

CTCF aligns single-cell TAD-like domain boundaries and stabilizes long-range active chromatin clusters.

CCCTC-binding factor (CTCF) is a key architectural protein in the three-dimensional (3D) genome, yet how its loss reshapes chromatin structure and transcription at single-cell resolution remains unclear. Using HiRES, which jointly profiles chromatin contacts and RNA from the same nucleus, we examined genome-wide effects of CTCF depletion. Topologically associating domain (TAD)-like domains (TLDs) across single cells remained largely unchanged in number and size after CTCF loss, but their boundaries became more variably positioned, and pseudobulk analyses revealed reduced interactions within A compartments. We also developed SALTAFinder to identify Spatially Aggregated Long-distance TLD Assemblies (SALTAs), clusters of TLDs occupying shared 3D space within single cells. A subset of SALTAs is enriched for highly expressed genes and super-enhancers and declines upon CTCF depletion. This structural reorganization coincided with a global reduction in per-cell RNA output, as indicated by HiRES and orthogonal measurements. Together, these findings suggest that CTCF contributes to the coordinated regulation of chromatin organization and transcriptional capacity and is associated with stabilization of long-range active chromatin clusters.

CCCTC-Binding Factor↗