GSE135834
Molecular maps of the Lamin B1-associated genomic regions in oligodendrocyte lineage cells
This study addresses the mechanisms regulating the identity of oligodendrocyte progenitor cells (OPC) in physiological conditions and the pathological mechanisms leading to autosomal  adrenoleukodystrophy (ADLD), a disease caused by persistence of lamin B1 (LMNB1) expression in oligodendrocytes (OL).  Using mouse primary OPCs and a novel technique for the study of DNA-protein interaction, we identify the genomic regions showing dynamic interactions with LMNB1.  The transition from ESC to OPC revealed increased association of gene involved in pluripotency and neuronal function and decreased association of gene categories associated with the differentiation of OPC into OL (including genes regulating epigenetic modifiers, RNA processing and protein phosphorylation).  Since LMNB1 declines during the transition from OPC to OL, and its persistent expression has been linked to pathological conditions, such as ADLD, we further identified the molecular maps of genome-lamina reorganization in OPC differentiating into OL which continue to express LMNB1 (mOLLMNB1).  The transition from OPC to mOLLMNB1 revealed increased association to LMNB1 of genomic regions encoding for lipid metabolism and protein phosphorylation, and decreased association of genes negatively regulating differentiation. These data highlight the importance of LMNB1 in physiological conditions and identify mechanisms responsible for late onset ADLD.  Overall design: Quantifying laminB-DNA association through DamID high throughout sequencing