Genome-Wide and Phase-Specific DNA-Binding Rhythms of BMAL1 Control Circadian Output Functions in Mouse Liver
(A) Top panel: Fraction of rhythmic BMAL1 sites in different subgroups. Sites were ranked according to binding strength using total number of tags over all the time points. Subgroups include all sites up to the indicated ranking. Lower panel: Histogram of binding phases peaks between ZT4 and ZT8. (B) Temporal profiles of BMAL1 binding ordered by phase. Only rhythmic profiles are plotted (Fisher test, p<0.05; see Materials and Methods). (C) Histogram of number of tags in BMAL1 binding sites for all sites (black curve) and a group of RCGs (grey bars), 63% of which (26 out of 41) are above the 95% quantile shown by the vertical dashed line. The RCGs include Per1/2/3, Cry1/2, Dec1/2, Rev-Erbα/β, Rorα/γ, E4bp4, and Hlf/Tef/Dbp, and show 41 binding sites all together. (D) BMAL1 ChIP-Seq data at the Dbp locus (visualized in the UCSC Genome Browser) show three rhythmic binding sites located at the promoter, in the first intron, and in the second intron. Notably, these overlap with DNase I hypersensitive sites , shown by the black arrows. The panels below show quantifications of BMAL1 binding. The scale is in number of non-redundant tags per 10 million mapped tags (see Materials and Methods). The PhastCons conservation score measures phylogenetic conservation among 20 placental mammals . (E) UCSC Genome Browser view of BMAL1 ChIP-Seq data at the Rev-Erbα locus, showing two circadian binding sites close to its promoter and one upstream (−8 kb) site.