ChAHP Displaces Transcriptional Regulators Through Active Chromatin Remodeling [RNAseq]

Transcriptional control in eukaryotes relies on the coordinated action of chromatin-based regulatory mechanisms, including control of nucleosome occupancy and chromatin modifications. We previously identified the ChAHP complex – comprising the chromatin remodeler CHD4, transcription factor ADNP, and HP1 proteins – as a repressor of SINE B2 retrotransposons and site-specific regulator of CTCF engagement with chromatin. However, the molecular basis of these functions remained unresolved. Here, we show that ChAHP-associated CHD4 is essential for SINE B2 repression, while HP1 proteins are dispensable. We further demonstrate that CHD4’s remodeling activity is not required for chromatin binding, but is critical for both retrotransposon silencing and efficient CTCF antagonism. We propose ChAHP is a sequence-specific recruiter of chromatin remodeling activity, facilitating transcriptional control and localized modulation of chromatin architecture. RNAseq experiments for ADNP PXVxL and N-terminal mutants and for CHD4-ADNP wt and mutant fusions were performed independent triplicates in wt and Cas9-engineered mESC.