Functional characteristics of a double positive feedback loop coupled with autorepression

Details Functional characteristics of a double positive feedback loop coupled with autorepression Functional characteristics of a double positive feedback loop coupled with autorepression

2009-02-11

arxiv.org/abs/0902.1881v1

Phys. Biol. 5 (2008) 046008 (9pp)

Biology

Quantitative Biology

Molecular Networks

9 pages 14 figures

Scientific paper

We study the functional characteristics of a two-gene motif consisting of a double positive feedback loop and an autoregulatory negative feedback loop. The motif appears in the gene regulatory network controlling the functional activity of pancreatic $\beta$-cells. The model exhibits bistability and hysteresis in appropriate parameter regions. The two stable steady states correspond to low (OFF state) and high (ON state) protein levels respectively. Using a deterministic approach, we show that the region of bistability increases in extent when the copy number of one of the genes is reduced from two to one. The negative feedback loop has the effect of reducing the size of the bistable region. Loss of a gene copy, brought about by mutations, hampers the normal functioning of the $\beta$-cells giving rise to the genetic disorder, maturity-onset diabetes of the young (MODY). The diabetic phenotype makes its appearance when a sizable fraction of the $\beta$-cells is in the OFF state. Using stochastic simulation techniques, we show that, on reduction of the gene copy number, there is a transition from the monostable ON to the ON state in the bistable region of the parameter space. Fluctuations in the protein levels, arising due to the stochastic nature of gene expression, can give rise to transitions between the ON and OFF states. We show that as the strength of autorepression increases, the ON$\to$OFF state transitions become less probable whereas the reverse transitions are more probable. The implications of the results in the context of the occurrence of MODY are pointed out..

Affiliated with

Also associated with

No associations

Rating

Functional characteristics of a double positive feedback loop coupled with autorepression does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.

If you have personal experience with Functional characteristics of a double positive feedback loop coupled with autorepression, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Functional characteristics of a double positive feedback loop coupled with autorepression will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFWR-SCP-O-487809