NFIL3 a protein that follows the winter season

Staining of NFIL3 (green) in nuclear bodies with DNA (blue) and microtubules (red) in A-431 cells.

Diurnal cycle influence biological processes in all organisms, on a molecular level, through regulators of the circadian clock. The Nuclear factor interleukin-3-regulated protein is a component of the circadian clock in humans that also fluctuates with the seasons. The Human Protein Atlas team has stained in A-431 cells NFIL3 (green) in nuclear bodies with DNA (blue) and microtubules (red).

Many human genes follow a so called circadian clock and research has shown that some of those genes themselves follow the seasons (Dopico et al. 2015). When winter is coming, you sense it and your genes know it too. Expression of one of those genes, NFIL3, peaks during December until February and has its lowest expression during the summer months.

NFIL3 is a transcriptional regulator involved in regulation of immune processes. Like many other transcription regulators it localizes to nuclear bodies as seen on the Cell Atlas images and binds to specific DNA motifs. The protein has a leucine zipper DNA-binding domain and binds as a homodimer to activating transcription factor sites including both cellular and viral promoters. Among other targets, it represses PER1 and PER2 expression which are known circadian clock regulators. In NFIL3-/- mice the normal circadian control on immune responses get deregulated causing increased susceptibility to inflammatory disease (Yu et al. 2013). Genetic variation in NFIL3 gene sequence has also been associated with human inflammatory bowel disease (Jostins et al. 2012).


Dopico et al. 2015, Widespread seasonal gene expression reveals annual differences in human immunity and physiology, Nature Communications 6, DOI: 10.1038/ncomms8000
Jostins et al. 2012, Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease, Nature 491, 119?124, DOI: 10.1038/nature11582
Yu et al. 2012, TH17 Cell Differentiation Is Regulated by the Circadian Clock, Science 342(6159) 727-730, DOI: 10.1126/science.1243884

Devin Sullivan