UNASSIGNED: The GLI transcription factors, @entity19990 , @entity27655 , and @entity20734 , transduce Hedgehog and non-hedgehog signals and are involved in regulating development and tumorgenesis. Surprisingly, they were recently found to modulate important functions of mature liver. However, less is known about their mutual interactions and possible target genes in mature hepatocytes. To get a deeper insight into these interactions cultured @entity19 hepatocytes were transfected with siRNAs against each GLI factor. RNA was extracted at different times and the expression levels of the genes of interest were determined by quantitative real-time PCR. The time-dependent data were analysed by a fuzzy logic-based modelling approach. The results indicated that the GLI factors constitute an interconnected network. @entity27655 inhibited @entity19990 expression and was coupled with @entity20734 by a positive feedback loop. The regulatory activity between @entity19990 and @entity20734 was more complex switching between a positive and a negative feedback loop depending on whether the level of @entity27655 is low or high, respectively. Generally, this network structure enables a dynamic behaviour. When @entity27655 is low, it may keep @entity19990 and @entity20734 activity balanced favouring the appropriate modulation of transcription factors like the Ppars and @entity4062 . When @entity27655 is high, it may prevent an uncontrolled amplification that may lead to @entity5 . In conclusion, the three GLI factors in mature hepatocytes form an interactive transcriptional network that is involved in the control of target genes associated with metabolic zonation as well as with lipid and drug metabolism. Its structure in mature cells seems different from embryonic cells.

Fuzzy modeling reveals a dynamic self-sustaining network of the GLI transcription factors controlling important metabolic regulators in adult XXXX hepatocytes.

@entity19 :: ('10090', 'Species') :: ['mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity4062 :: ('20787(Tax:10090)', 'Gene') :: ['Srebp1'] @entity27655 :: ('14633(Tax:10090)', 'Gene') :: ['GLI2'] @entity19990 :: ('14632(Tax:10090)', 'Gene') :: ['GLI1'] @entity20734 :: ('14634(Tax:10090)', 'Gene') :: ['GLI3']
@entity19 :: (10090,Species) :: ['mouse']
