Transcriptional regulatory logic of the diurnal cycle in the mouse liver
Fig 5
Chromatin accessibility in Bmal1-/- mice at ZT6 is generally similar as in the Wild-Type (WT) mice but is lower at BMAL1 sites.
A. The Rev-erbα (left) and Gsk3a (right) promoters. DNase I signal (in red) is strongly reduced in Bmal1-/- mice at sites bound by CLOCK:BMAL1 in WT mice (BMAL1 chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) signal in blue) in the Rev-erbα promoter but is similar in WT and Bmal1-/- mice at the Gsk3a promoter that are not bound by BMAL1. The vertical scale is the same for all three DNase I tracks, as well as for both BMAL1 ChiP-seq tracks. Wild-type ZT18 signals are lower (about half) than at ZT6 in both genes but not as low as in the Bmal1-/- mice. B. Comparison of DNase I signals at ZT6 in Bmal1-/- versus WT mice. All DNase I hypersensitive sites (DHSs) overlapping BMAL1 ChIP-seq peaks in [17] are shown (n = 1,555). The dashed lines indicate 4-fold difference. C. Boxplots showing DNase I intensity at the same sites as in B, at peak (ZT6) and trough (ZT18) activities of BMAL1 in the WT, and at ZT6 in Bmal1-/- mice for all BMAL1-binding sites (green), BMAL1 sites with an associated expression phase between ZT2 and ZT10 (orange), and with a tandem E-box (grey). All pairwise comparisons (within the same color) between either ZT6 versus ZT18 or ZT6 versus ZT6 Bmal1-/- are significant (p < 0.001). D–E. Same as B–C but using overlap with USF1 ChIP-seq peaks [74] to select DHSs (n = 1,705).