ChAHP (Adnp, Chd4, HP1) mediates sequence-specific recruitment of HP1 independent of H3K9 methylation. Mus musculus

Activity-dependent neuroprotective protein (ADNP) is one of the most frequent autism spectrum disorder-associated gene products known to date. Here we show that Adnp interacts with the chromatin remodeler Chd4 and the heterochromatin protein HP1 to form a stable complex, which we refer to as ChAHP. Genetic ablation of ChAHP components or DNA binding sites in embryonic stem cells prematurely activates lineage-specific genes, revealing an important role for Adnp in restraining the differentiation capacity of pluripotent cells. Adnp targets the ChAHP complex to specific sequence motifs at euchromatic loci, representing an H3K9 methylation-independent mechanism of HP1 recruitment and gene silencing. Overall design: ChIP-seq, RNA-seq and ATAC-seq experiments were performed in mouse ES cells of isogenic background, each experiment was performed in biological replicates. Please note that each bed file (linked to the Series records) belongs to the following samples; Adnp_peak_positions.bed: ChIPseq for Adnp in wt mES cells rep1-3 [GSM2582357-GSM2582359] HP1g_peaks_wo_Adnp_motif_positions.bed: ChIPseq for HP1g in wt mES cells rep1-3 [GSM2582375-GSM2582377], ChIPseq for HP1g (Cbx3) in Adnp knock-out mES cells rep1-3 [GSM2582389-GSM2582391]