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Yan Song

Publications and source records attributed to Yan Song.

2 recordsLinked to original sources

Stepwise allelic trajectory of ETP2 underlies trade-off between UVB tolerance and submergence adaptation in Arabidopsis thaliana.

Strong UVB radiation critically restricts plant growth, yield, and distribution, while mechanisms enabling adaptation to intense UVB remain unclear. Here, we uncover that the F-box ubiquitin E3 ligase UVBT1 (also known as ETP2) is indispensable for UVB tolerance in A. thaliana. In the high-altitude Tibet accession, a distinctive 166-bp deletion in ETP2 promoter leads to the complete absence of the W-box element, thereby eliminating WRKY36-mediated transcriptional repression. This results in elevated ETP2 levels, which degrade EIN2 and activate the protective anthocyanin/flavonoid pathway. Conversely, in low-altitude accessions, which are often exposed to lower UVB and higher precipitation conditions, WRKY36-mediated repression of ETP2 stabilizes EIN2 and WRKY22, endowing the plants with submergence tolerance. Notably, aside from the Tibet-accession-specific 166-bp deletion, the geographical distribution of the promoter allelic shift from C to G near the ETP2 W-box within the 166-bp region is tightly associated with UVB radiation with increasing altitudes for the other global accessions. This allelic change also enhances WRKY36-mediated repression of ETP2, suggesting an additional stepwise adaptation process. This work thus defines the WRKY36-ETP2-EIN2/WRKY22 module as a key regulator of UVB tolerance and submergence adaptation, potentially enabling A. thaliana to adapt to environments with varying UVB and precipitation conditions.

Arabidopsis

Comprehensive assessment of homologous recombination deficiency via simultaneous methylation and mutation analysis in epithelial ovarian cancer: implications for PARP inhibitors efficacy.

BACKGROUND: The advent of poly (ADP-ribose) polymerase inhibitors (PARPi) over the past decade has significantly altered the management of epithelial ovarian cancer (EOC). We proposed that the etiology of homologous recombination deficiency (HRD) might underlie the variable responses to PARPi observed across patient populations. METHODS: As part of the phase 2 study of the Chinese HRD Harmonization Project, we developed a genomic methylation sequencing (GM-seq) pipeline facilitated by the TET enzyme for the simultaneous identification of methylated modifications and genetic variations in EOC tumor samples, and compared with established DNA sequencing-based HRD assays. RESULTS: Somatic mutation and HRD scores were confounded by low tumor purity in our cohort of 98 locally advanced/advanced EOC patients. In samples with tumor purity&#x2009;&#x2265;&#x2009;30% (n&#x2009;=&#x2009;45), the GM-seq pipeline showed high consistency with DNA sequencing-based HRD assay, identifying genetic variations in homologous recombination repair (HRR) genes and HRD score with 92.6% (25/27) and 97.1% (33/34) consistency respectively, in addition to conducting methylation profiling. Moreover, different underlying mechanisms of HRD were associated with varying degrees of PARPi efficacy, with BRCA1/2 LOH group having the best efficacy (median PFS, undefined), followed by BRCA1 methylation group (median PFS, 23.4 months), and those with unknown etiology of HRD having the worst efficacy (median PFS, 8.8 months, p&#x2009;<&#x2009;0.001). CONCLUSION: Our findings underscore the importance of considering HRD etiology when evaluating PARPi efficacy in EOC patients. The GM-seq pipeline, represents a significant advancement in HRD detection, enabling more accurate predictions of PARPi response.

Epithelial ovarian cancer (EOC)