Mammalian ISWI and SWI/SNF selectively mediate binding of distinct groups of transcription factors (ChIP-seq data sets)

Remodelers define nucleosome composition, presence and position. Mammalian imitation-switch-type (ISWI) comprise one class, mostly relying on the ATPase Snf2h for activity. We show that embryonic stem cells are viable without Snf2h, enabling to study its function and contrast it to Brg1, the ATPase of SWI/SNF. Loss of Snf2h specifically affects nucleosomal positioning and increases linker lengths genome-wide providing in vivo evidence for ISWI function in ruling nucleosomal spacing. Systematic analysis of transcription factor binding reveals selective requirement on either remodeling activity. One group, containing the transcriptional repressor REST depend on BRG1, while a non-overlapping set including the insulator protein CTCF, relies on Snf2h. Importantly localized reduction in CTCF binding decreases long-range interactions. Collectively, this links mammalian ISWI to nuclear organization, demonstrates its cellular role for nucleosomal periodicity and reveals that transcription factors rely on specific remodeling pathways for proper genomic binding. Overall design: ATAC-seq (14, 2 or 3 replicates per condition), Bis-seq (4, single replicate per condition), ChIP-seq (18 CTCF and 20 REST, 1 or 2 replicates per condition), HiC-seq (8, two replicates per condition), MNase-seq (8, 2 replicates per condition) and RNA-seq (18, 2 to 5 replicates per condition) profiling of mouse embryonic stem cells of wildtype, Snf2h ko, Snf2h ko/add-back (wildtype and mutant) and Brg1 ko genotypes.