Splice isoforms of the histone variants macroH2A1 differentially regulate hippocampal gene expression and memory formation

Histone variants are critical components of neural chromatin and emerging regulators of long-term memory formation and neural gene expression. We previously showed that deleting the macrodomain-bearing histone macroH2A1 in mouse hippocampus impairs long-term memory. Here, we expand on this finding by discriminating between alternative splice isoforms of mH2A1, mH2A1.1 and mH2A1.2, which bear structurally distinct macrodomains. We characterized the genomic localization of mH2A1.1 and mH2A1.2 using isoform-specific antibodies, and evaluated the effects of isoform-specific knockdown via shRNA on hippocampal transcription and hippocampal-dependent memory.