Abstract:
Circadian clocks drive the rhythmic expression of ~5-15% of expressed genes in
mammals in a cell-type and tissue-specific manner. Nuclear envelope, a global
regulator of the genome, interact with the circadian core-clock transcription factor
BMAL1 through Man1. LBR and lamin B1 were also found to have similar regulatory
roles as Man1 in regulating rhythmic gene expression. We hypothesize that B-type
lamins and especially lamin B2 might modulate and have regulatory roles in clock
function. Further studies also show that the expression profiles of the circadian
genes differ in human colorectal cells from that of mouse embryonic fibroblasts
(MEFs). Therefore clock disruption in MEFs may not be translated to clock disruption
in human colorectal cancer cells. We also find that while AKT2 and KRAS show
fluctuations in their expression levels across time, SNAI1 and RUNX2 levels are
relatively constant. The nuclear envelope is likely to associate and regulate core
circadian clock genes and maintain the periodicity of clock-controlled genes in cells.
