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Di Wang

Publications and source records attributed to Di Wang.

4 recordsLinked to original sources
PubMed2026

hnRNPK condensates facilitate enhancer-promoter looping and RNA polymerase II recruitment.

Enhancer RNAs interact with promoter-derived RNAs to dictate enhancer-promoter looping, but the RNA-binding protein that mediates this process has remained unidentified. Here we identify hnRNPK as a general structural regulator that preferentially binds to nascent RNAs transcribed from enhancer and promoter regions, promoting enhancer-promoter looping and transcriptional activation. We further show that hnRNPK forms phase-separated, cavity-containing condensates that encapsulate RNA polymerase II (Pol II) via its RPB3 subunit, facilitating chromatin looping and potentially enabling recruitment of Pol II from enhancers to promoters through protein dimerization. Notably, a mutation associated with Au-Kline syndrome in hnRNPK (c.953+1dupG) alters its condensates from a liquid-like to a gel-like state, leading to developmental defects in knock-in mice. Fibroblasts derived from these mutants display reduced enhancer-promoter looping and decreased Pol II recruitment at promoters of key developmental genes. These findings suggest that hnRNPK is a structural regulator of enhancer-promoter communication and highlight the importance of RNA-RNA interactions mediated by RNA-binding proteins in transcriptional regulation.

RNA Polymerase II↗
PubMed2026

Paired genomic profiling of primary tumor and lymph-node metastases identifies candidate prognostic features in penile squamous cell carcinoma.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited genomic data in Asian populations. Lymph node metastasis heavily dictates prognosis, yet molecular determinants of progression remain poorly understood. We aimed to characterize the genomic landscape and explore candidate prognostic genomic features using paired primary and metastatic PSCC tumors. PATIENTS AND METHODS: Targeted next-generation sequencing (437 cancer-related genes) was performed on primary tumors and matched lymph node metastases from 20 Chinese patients. Somatic alterations, intralesional heterogeneity, and tumor mutation burden (TMB) were analyzed and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: The most frequent primary tumor mutations included TP53 (45%) and TERT (40%). Notably, CCND1/FGF19 co-amplification (20% of cases) was associated with inferior DFS (P = .027) and showed a trend toward shorter OS (P = .050). Conversely, T-cell receptor (TCR) pathway alterations correlated with markedly improved survival. Comparing paired lesions revealed 59.8% shared alterations. Elevated TMB in metastases relative to matched primary tumors was significantly associated with poorer DFS (P = .008), while higher intralesional heterogeneity showed a trend toward worse OS. CONCLUSION: Paired profiling revealed broadly conserved genomic features together with lesion-specific divergence in PSCC. Recurrent CCND1/FGF19-containing 11q13 amplification, TCR pathway alterations, and elevated metastatic TMB warrant evaluation as potential prognostic features in larger, independently validated cohorts with integrated HPV and immune profiling.

Humans↗
PubMed2026

Functions of tandem-repeat galectins and domain coordination governs galectin-4 activity in grass carp (Ctenopharyngodon idella).

Galectins are β-galactoside-binding lectins that play essential roles in innate immunity. Among them, tandem-repeat galectins (TrGals), typically composed of two distinct carbohydrate-recognition domains (CRDs) connected by a linker peptide, are well established as key regulators of pathogen recognition and host defense in mammals. However, their structural diversity and immunological functions in teleost fish remain poorly understood. In this study, five TrGals (Gal-4, Gal-8a, Gal-8b, Gal-9, and Gal-9like) were identified in grass carp. Sequence and structural analysis revealed that Gal-8a/b, Gal-9, and Gal-9like possess the canonical two-CRD architecture, whereas Gal-4 uniquely contains four highly similar tandem-repeat domains. All five TrGals were broadly expressed across examined tissues, with predominant expression in the liver. Upon Aeromonas hydrophila infection, Gal-4, Gal-8a, Gal-8b, and Gal-9 were rapidly up-regulated at early time points (3-6 h). To elucidate the functional significance of CRD number, recombinant full-length CiGal-4 (CiGal4-full) and three truncated variants containing one, two, or three CRDs (CiGal4-1CRD, CiGal4-2CRD, and CiGal4-3CRD) were generated and systematically characterized. All recombinant proteins contained the conserved β-sheet structure typical of galectin CRDs. Functional assays revealed that CiGal4-full displayed the strongest growth-inhibitory activity against all tested bacteria, whereas CiGal4-1CRD showed the weakest effect. Notably, CiGal4-2CRD exhibited the most potent bactericidal activity, surpassing the full-length protein, while CiGal4-3CRD showed no further enhancement. CiGal4-full and CiGal4-2CRD showed superior carbohydrate-binding activities compared with the other variants. Collectively, these results reveal that CRD copy number alone does not linearly determine galectin function. Instead, domain organization and conformational coordination are critical for optimizing antimicrobial activity. This study provides new insights into the structure-function relationships and evolutionary diversification of galectins in teleosts and highlights their potential as novel antimicrobial and immunomodulatory agents in aquaculture.

Animals↗
PubMed2024

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

INTRODUCTION: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized. METHODS: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. RESULTS: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. HIGHLIGHTS: Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water-corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non-carriers.

Humans↗