Christiane Wirbelauer

May 30, 2024 | nature.com | Mario Iurlaro |Francesca Masoni |Ilya M. Flyamer |Christiane Wirbelauer |Murat Iskar |Lukas Burger | +2 more

Catalytic activity of the imitation switch (ISWI) family of remodelers is critical for nucleosomal organization and DNA binding of certain transcription factors, including the insulator protein CTCF. Here we define the contribution of individual subcomplexes by deriving a panel of isogenic mouse stem cell lines, each lacking one of six ISWI accessory subunits. Individual deletions of subunits of either CERF, RSF, ACF, WICH or NoRC subcomplexes only moderately affect the chromatin landscape, while removal of the NURF-specific subunit BPTF leads to a strong reduction in chromatin accessibility and SNF2H ATPase localization around CTCF sites. This affects adjacent nucleosome occupancy and CTCF binding. At a group of sites with reduced chromatin accessibility, CTCF binding persists but cohesin occupancy is reduced, resulting in decreased insulation. These results suggest that CTCF binding can be separated from its function as an insulator in nuclear organization and identify a specific role for NURF in mediating SNF2H localization and chromatin opening at bound CTCF sites. Systematic deletions of individual imitation switch (ISWI) subunits in mouse embryonic stem cell lines highlight the role of BPTF in regulating chromatin accessibility at most CTCF sites and binding at a subset, with a modest effect on its insulating function.