HMGN1 and HMGN2 are recruited to acetylated and histone variant H2A.Z-containing nucleosomes to regulate chromatin state and transcription

The High Mobility Group Nucleosome-binding (HMGN) proteins are small abundant nuclear proteins that directly bind nucleosomes and constitute a major component of chromatin. HMGN proteins specifically localize to enhancers and actively transcribed genes across the genome, however the roles of HMGN proteins in regulating chromatin structure and transcription remain poorly understood. To investigate the localization and function of HMGN proteins on chromatin, we engineered mouse embryonic stem cells (mESCs) lacking HMGN1 and/or HMGN2 (Hmgn1-/- mESCs, Hmgn2-/- mESCs, and Hmgn1-/-Hmgn2-/- mESCs) and profiled gene expression and localization of architectural proteins. Gene expression was profiled in WT mESCs, Hmgn1-/- mESCs, Hmgn2-/- mESCs, and Hmgn1-/-Hmgn2-/- mESCs via RNA-sequencing. Overall design: RNA-seq was performed in wildtype mESCs, Hmgn1-/- mESCs, Hmgn2-/- mESCs, and Hmgn1-/-Hmgn2-/- mESCs in triplicate replicates.