ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/018/SRR29457718/SRR29457718_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/017/SRR29457717/SRR29457717_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/014/SRR29457714/SRR29457714_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/013/SRR29457713/SRR29457713_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/014/SRR29457714/SRR29457714_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/015/SRR29457715/SRR29457715_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/017/SRR29457717/SRR29457717_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/016/SRR29457716/SRR29457716_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/013/SRR29457713/SRR29457713_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/016/SRR29457716/SRR29457716_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/015/SRR29457715/SRR29457715_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR294/018/SRR29457718/SRR29457718_1.fastq.gzprimaryOK200GenomicsFujian Medical Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1125303Inhibition 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_CUT&Tag2024-06-232024-06-23PRJNA1125303