Mezigdomide reverses T cell exhaustion through degradation of Aiolos/Ikaros and reinvigoration of cytokine production pathways [scATAC-seq]

Given the well-established notion that T cells undergo significant changes in their nuclear architecture and chromatin accessibility between different stages of differentiation or phenotypic stage such as activation and exhaustion, we aimed to investigate the chromatin binding patterns of the Ikaros transcription factor, which plays a crucial role in T cell biology and gene regulation, including development, differentiation and activation in response to TCR stimulation. However, a thorough genome-wide analysis of its occupancy and transcriptional regulatory activity between T cell activation and exhaustion has not been performed. To address this, we conducted an integrated epigenomic investigation utilizing Hi-C, ATAC-seq, RNA-seq and ChIP-seq, focusing on Ikaros and histone modifications, including H3K27ac, H3K4me1, and H3K4me3. This approach allows us to understand Ikaros-specific regulation of transcription by characterizing the epigenome in Tact versus Tex cells.