ADNP is not a loop extrusion barrier and masks underlying CTCF motifs. Loss of ADNP exposes additional CTCF binding sites and leads to novel loop anchor formation
The organization of chromatin in the three-dimensional space is complex and requires the help of many proteins, including CTFC. Researchers from the group of Marc Bühler have identified a new player in the process: the transcription factor ADNP. In a recent study, they show that ADNP competes with CTFC, acting as a local modulator of chromatin looping. In a 2018 study , the Bühler group described a previously unknown protein complex called ChAHP, made up of the proteins HP1, CHD4, and ADNP (activity-dependent neuroprotective protein); the latter is a transcription factor that is essential for embryonic development and - when mutated - is involved in the Helsmoortel-Van der Aa syndrome, a complex neurological developmental disorder. The FMI scientists uncovered the gene silencing role of ChAHP and showed that, when the complex is inactivated due to a mutation in ADNP, genes get mistakenly expressed - thereby taking a major step towards elucidating the mechanisms underlying Helsmoortel-Van der Aa syndrome. Fabio Mohn and Lucas Kaaij from the Bühler group built on that study to understand the function of ADNP (as part of the ChAHP complex) in the context of chromatin organization in mouse embryonic stem cells. Their study has recently been published in Cell .
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