These discordant alterations strongly implicate disruption of the normal regulation of these genes.
The CTCF/RAD21 binding patterns may implicate disruption of cohesin function as either the cause or consequence of cluster 2 methylation at a subset of UC DMRs.
Although TGFβ is known to modulate DC maturity, 18 our studies implicate disruption of TGFβ signalling in DCs as a critical event in the development of autoimmunity.
We identified the up-regulation of miR-328, which also potentially targets MeCP2, perhaps implicating the disruption of neurodevelopmental regulatory circuits is a feature of prion disease.
Studies interrogating CpG islands not associated with recognized imprints reported methylation at numerous sites to be associated with sperm quality, implicating widespread disruption of DNA methylation in abnormal spermatogenesis (Houshdaran et al. 2007; Pacheco et al. 2011).
14 Furthermore, although this hypothesis implicating a disruption in the cholesterol synthesis pathway seems generally plausible, it does not explain why patients with hereditary hypocholesterolemia who are on statins do not report the occurrence of myopathy in the same way.
The loss of intact titin has been demonstrated in failing human hearts, implicating titin disruption in the pathogenesis of progressive ventricular dysfunction (Wang et al, 1988; Helmes et al, 1996, 2003).
Subsequent studies have also identified increases in both the transcript abundance and activity of these proteases, implicating the disruption of specific signaling pathways (Metcalf et al., 2009; Metcalf et al., 2010).
Empirical data continue to mount implicating these disruptions as components of the pathophysiology of the illness (Gonzalez 2014).
It is implicated in disruption of DNA methylation, histone acetylation and disturbance of miRNA binding (192, 224, 225), redox signaling (226) and induction of micronuclei through spindle defects in mitosis (227).
