Abstract
The access of Transcription Factors (TFs) to their cognate DNA binding motifs requires a precise control over nucleosome positioning. This is especially important following DNA replication and during mitosis, both resulting in profound changes in nucleosome organization over TF binding regions. Using mouse Embryonic Stem (ES) cells, we show that the TF CTCF displaces nucleosomes from its binding site and locally organizes large and phased nucleosomal arrays, not only in interphase steady-state but also immediately after replication and during mitosis. Correlative analyses suggest this is associated with fast gene reactivation following replication and mitosis. While regions bound by other TFs (Oct4/Sox2), display major rearrangement, the post-replication and mitotic nucleosome positioning activity of CTCF is not unique: Esrrb binding regions are also characterized by persistent nucleosome positioning. Therefore, selected TFs such as CTCF and Esrrb act as resilient TFs governing the inheritance of nucleosome positioning at regulatory regions throughout the cell-cycle.
Highlights
Gene regulatory processes are frequently governed by sequence-specific Transcription Factors (TFs) that recognize specific DNA binding motifs enriched at promoters and enhancers (Spitz and Furlong, 2012)
The Nucleosome Depleted Regions (NDRs) and the positioning of the +/- 1 and surrounding nucleosomes were more prominent immediately after replication than after 1 hr (Figure 4A). This suggests that following replication, Esrrb is rapidly rebound at these sites and imposes strong nucleosome positioning, which is subsequently modified by the binding of additional TFs – a phenomenon that we previously described when we compared Esrrb binding in interphase and mitosis (Festuccia et al, 2019)
We have studied the functional relationships between TF binding and nucleosome positioning during replication and mitosis, using CTCF as a paradigmatic example
Summary
Gene regulatory processes are frequently governed by sequence-specific Transcription Factors (TFs) that recognize specific DNA binding motifs enriched at promoters and enhancers (Spitz and Furlong, 2012). Whereas nucleosomal DNA is accessible to pioneer TFs (Cirillo, 1998; Zaret and Carroll, 2011), other TFs require co-factors to evict or displace nucleosomes that occlude their binding sites. These co-factors can be additional TFs that act cooperatively to destabilize nucleosomes (Mirny, 2010; Miller and Widom, 2003), and/or ATP-dependent activities that slide or evict nucleosomes and remodel cis-regulatory elements (Becker and Workman, 2013; Li et al, 2014). This is well illustrated by the genomic binding sites of the zinc
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