YBX1 indirectly targets heterochromatin-repressed inflammatory response genes through binding to CBX5 [PAR-CLIP]

The RNA- and DNA-binding protein YBX1 is involved in various cellular processes. We here focused on investigating its role in posttranscriptional gene regulation in medulloblastoma, in which CRISPR screens have shown its essentiality for cellular survival. We found that YBX1 knockdown leads to broad upregulation of genes related to neuroinflammation, and directly regulates mRNA stability of various mRNA targets. More specifically, target CBX5, also called heterochromatin-protein 1 alpha (HP1-alpha), is downregulated upon YBX1 KD. It associates strongly with heterochromatin, and upon downregulation allows for upregulation of heterochromatin repressed genes related to inflammation. Overall design: We performed survival assays and RNA-seq upon YBX1 knockdown to elucidate the role of transcriptional control of YBX1 in medulloblastoma. Differential expresion analysis and pathway analysis elucidated the role of YBX1 in transcriptional control. We further performed PAR-CLIP of YBX1 to identify direct binding targets, and integrated results with differential expression analysis. Please note that processed data was generated from both replicates and is linked to the rep1 sample records.