Journal: Neurobiology of Sleep and Circadian Rhythms

Article Title: The PER2:BRCA1:POU2F1(OCT-1) ternary complex represents a multi-component scaffold model for circadian gene regulation

doi: 10.1016/j.nbscr.2025.100141

Figure Lengend Snippet: PER2 integrates circadian and transcriptional signals at the mouse Esr1 promoter. ( A ) Time-course expression profiles of Esr1 and Per2 mRNA showing circadian oscillations in multiple mouse tissues. Wild-type mice were entrained to 12-h light:12-h dark cycles for one week, then released into constant darkness. Tissues (white adipose tissue, liver, and kidney) were collected at 2 h intervals for 48 h mRNA expression levels (normalized counts) are plotted against circadian time (CT). Fitted cosine curves (blue for Esr1 , red for Per2 ) show that both genes oscillate with similar periodicity across tissues, with tissue-specific phase relationships. ( B ) Quantitative circadian parameters (period, phase, amplitude, and baseline expression) determined by meta2d analysis of data shown in panel A. Upper table. Circadian periods for Esr1 and Per2 in each tissue show remarkable similarity (white adipose: ∼24.2 h for both; liver: ∼23.8 h Esr1 , ∼23.5 h Per2 ; kidney: ∼24.1 h for both). Lower table. Phase analysis reveals tissue-specific phase relationships: Esr1 leads Per2 by 2–4 h in white adipose tissue and kidney, while lagging by ∼1–2 h in liver. P-values (p < 0.01) confirm statistically significant rhythmicity for both genes in all tissues. ( C ) Per2 and Esr1 circadian rhythms are abolished in Per1 −/− / Per2 −/− double knockout mice. Liver expression data from wild-type and Per1/2 dKO mice ( GSE171975 ) show that in wild-type liver, both Per2 and Esr1 exhibit robust circadian oscillations (period ∼23 h, p < 0.01). In contrast, both genes completely lose rhythmicity in Per1/2 dKO liver tissue, with expression remaining flat across all time points. Importantly, basal transcript levels are maintained despite loss of oscillation, demonstrating that Esr1 transcription per se does not require functional PER proteins, but rather that circadian modulation of expression requires clock function. ( D ) Pou2f1 and Brca1 transcripts show no circadian rhythmicity at the mRNA level. Upper panel: Pou2f1 expression remains relatively constant across the circadian cycle in both wild-type and Per1/2 dKO liver, with no statistically significant oscillations. Lower panel: Brca1 expression similarly lacks circadian rhythmicity in both genotypes. These non-rhythmic expression patterns contrast sharply with the robust oscillations observed for Per2 and Esr1 , suggesting that constitutively expressed POU2F1(OCT-1) and BRCA1 serve as stable scaffolding factors that cooperate with rhythmically expressed PER2 to impose circadian control on Esr1 transcription. ( E ) Meta2d analysis results for Brca1 and Pou2f1 showing circadian parameters and statistical assessment. p-values confirm the absence of significant circadian rhythmicity (p > 0.01) for both genes in both wild-type and Per1/2 dKO animals. ( F ) Direct temporal comparison of Per2 and Esr1 oscillations in wild-type and Per1/2 dKO liver. Per2 (red) and Esr1 (blue) expression from GSE171975 are plotted together to visualize their temporal relationship.

Article Snippet: Circadian gene expression datasets were obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database.

Techniques: Expressing, Double Knockout, Functional Assay, Scaffolding, Control, Comparison