ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/069/SRR26394569/SRR26394569_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/081/SRR26394581/SRR26394581_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/083/SRR26394583/SRR26394583_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/071/SRR26394571/SRR26394571_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/075/SRR26394575/SRR26394575_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/073/SRR26394573/SRR26394573_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/084/SRR26394584/SRR26394584_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/085/SRR26394585/SRR26394585_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/076/SRR26394576/SRR26394576_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/072/SRR26394572/SRR26394572_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/080/SRR26394580/SRR26394580_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/074/SRR26394574/SRR26394574_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/068/SRR26394568/SRR26394568_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/084/SRR26394584/SRR26394584_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/078/SRR26394578/SRR26394578_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/072/SRR26394572/SRR26394572_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/079/SRR26394579/SRR26394579_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/083/SRR26394583/SRR26394583_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/075/SRR26394575/SRR26394575_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/069/SRR26394569/SRR26394569_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/077/SRR26394577/SRR26394577_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/078/SRR26394578/SRR26394578_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/070/SRR26394570/SRR26394570_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/082/SRR26394582/SRR26394582_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/081/SRR26394581/SRR26394581_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/079/SRR26394579/SRR26394579_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/085/SRR26394585/SRR26394585_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/082/SRR26394582/SRR26394582_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/080/SRR26394580/SRR26394580_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/074/SRR26394574/SRR26394574_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/068/SRR26394568/SRR26394568_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/076/SRR26394576/SRR26394576_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/077/SRR26394577/SRR26394577_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/073/SRR26394573/SRR26394573_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/070/SRR26394570/SRR26394570_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/071/SRR26394571/SRR26394571_2.fastq.gzprimaryOK200GenomicsThe Trustees of Columbia University in the City of New Yorkhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1028534Homo sapiensGenomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection. However, cancer cells often evade these responses by overexpressing immune checkpoint regulators, such as PD-L1. Here, we identify the SNF2-family DNA translocase SMARCAL1 as a factor that favors tumor immune evasion by a dual mechanism involving both the suppression of innate immune signaling and the induction of PD-L1-mediated immune checkpoint responses. Mechanistically, SMARCAL1 relieves endogenous DNA damage and suppresses cGAS-STING-dependent signaling during cancer cell growth. Simultaneously, it cooperates with the AP-1 family member JUN to maintain chromatin accessibility at a transcriptional regulatory element in the PD-L1 gene, thereby promoting PD-L1 expression in cancer cells. SMARCAL1 loss hinders the ability of tumor cells to induce PD-L1 in response to genomic instability, enhances anti-tumor immune responses and sensitizes tumors to immune checkpoint blockade in a mouse melanoma model. Collectively, these studies uncover SMARCAL1 as a promising target for cancer immunotherapy. Overall design: Cleavage under targets and Release using nuclease (Cut-and-Run), for the chromatin profiling of SMARCAL1, JUN, H3K4me3 and H3K24me3 proteins in MDA-MB-436 cell lines treated as indicated.xref:PubMed:38301646ENAfalseSMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion [CUT&RUN]SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion [CUT&RUN]2025-09-242024-01-26PRJNA1028534GSE245448960638301646