ADNP Controls Gene Expression Through Local Chromatin Architecture by Association With BRG1 and CHD4

摘要: ADNP (Activity Dependent Neuroprotective Protein) is proposed as a neuroprotective protein whose aberrant expression has been frequently linked to rare neural developmental disorders and cancers, including the recently described neurodevelopmental Helsmoortel-Van der Aa syndrome. Recent studies have suggested that functions an important chromatin regulator. However, how ADNP-regulated mechanisms control gene stem cell fate commitment remains unclear. Here we show interacts with two remodelers, BRG1 CHD4. required for proper establishment of accessibility, nucleosome configuration, bivalent histone modifications genes. Loss leads enhancer over-activation increased ratio H3K4me3/H3K27me3 at key primitive endoderm (PrE) promoters, resulting in prominent up-regulation these genes priming ES differentiation toward endodermal types. Thus, our work revealed role local landscape structure by association These findings provide further insights into pathology