Epigenomic Profiling of H3K4me2 and H3K4me3 in Patient-Derived NPCs to Study L2HGDH Deficiency
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) was performed to investigate the epigenetic landscape in neural progenitor cells (NPCs) derived from L2HGA patient iPSCs with or without correction of the pathogenic L2HGDH variant. We profiled histone modifications H3K4me2 and H3K4me3 as well as input control across four conditions: unedited Patient 1 NPCs, corrected Patient 1 NPCs, corrected NPCs treated with DMSO, and corrected NPCs treated with the KDM5 inhibitor C70. This dataset provides insight into enhancer and promoter activity at the MYC locus and genome-wide effects of L-2HG-associated epigenetic dysregulation. Overall design: The study includes ChIP-seq analysis of 12 samples: three biological replicates each for input, H3K4me2, and H3K4me3 across four treatment groups—unedited NPCs, corrected NPCs, corrected NPCs + DMSO, and corrected NPCs + KDM5-C70. Immunoprecipitated DNA was sequenced on an Illumina platform. Peaks were called and differential enrichment analysis was performed to identify epigenetically dysregulated loci associated with L-2HG metabolism.