ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/028/SRR29695428/SRR29695428_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/027/SRR29695427/SRR29695427_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/026/SRR29695426/SRR29695426_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/031/SRR29695431/SRR29695431_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/030/SRR29695430/SRR29695430_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/026/SRR29695426/SRR29695426_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/028/SRR29695428/SRR29695428_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/027/SRR29695427/SRR29695427_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/031/SRR29695431/SRR29695431_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR296/030/SRR29695430/SRR29695430_2.fastq.gzftp://primaryOK200GenomicsFujian Medical Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1131099Inhibition of the assembly of the RBPJ transcription complex is known to alleviate T cell exhaustion by suppressing PDL1 expression. However, the role of RBPJ in T cells, especially whether inhibition of the assembly of the RBPJ transcription complex is involved in the anti-tumor activity of T cells, remains largely unknown. In this study, we used co-immunoprecipitation to identify HUWE1 as the E3 ubiquitin ligase for RBPJ combined application of CUT&amp Tag, ChIP/ATAC-qPCR, co-immunoprecipitation and flow cytometry indicated that RBPJ led to T cell dysfunction by reshaping the epigenetic landscape, enhancing the transcriptional activity or histone methylation/acetylation of exhausted genes finally, virtual screening and molecular dynamics simulation were used to find that Acarbose reshaped the assembly of the RBPJ-RUVBL1/DNA ternary complex to disrupt the function of RBPJ. Our results not only revealed the mechanism by which RBPJ expression was induced in exhausted T cells, but also explained the molecular mechanism of how RBPJ exacerbated T cell exhaustion. Furthermore, the molecular conformational shaping of the RBPJ transcriptional complex by Acarbose provided new insights into the role of targeted inhibition of T cell exhaustion in the treatment of hepatocellular carcinoma.ENAfalseEpigenetic landscape remodeled by the transcription factor RBPJ promotes tumor-infiltrating T cell exhaustion_ScRNA-Seq2024-07-092024-07-09PRJNA1131099