Identification of Myt1 as a subunit of the neural cell type-specific LSD1 complex. Mus musculus

Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. Recently, dynamic epigenomic regulation, including chromatin remodeling and histone modifications by transcriptional coregulator complexes, has been shown to be involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell-type and developing stage-specific activity is largely unknown. In this study, we aimed to isolate the histone demethylase LSD1 complex from neural cells by biochemical purification. In so doing, we identified MyT1 as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed several genes, including PTEN, that were directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation. Overall design: Neuro2a cells were treated with either siControl, siLSD1 or siMyT1 for 48 h (n=3)