Indeed, diverse mechanisms exist to mediate allelic inactivation including interplay of DNA modifications by DNA methylation and modifications of the histone proteins by acetylation, methylation, SUMOylation or phosphorylation [ 44, 45].
Furthermore, the complexity of post-translational modifications of p53 needs to be taken into consideration to reveal the functional significance of the single modifications as well as the sequential interplay of different modifications [38].
In Arabidopsis, TOPLESS, ABI-like, and AtARP4 illustrate the interplay of chromatin modifications and TF shuttling [154] [156].
The interplay of strain modification and doping effects is separated.
More recently, conjugation by SUMO has been suggested to play an additional role of antagonizing the effect of ubiquitin conjugation an evolution that appears to suggest a complex interplay of protein modification above that of simply activating and inactivating a protein [49], [50].
Subsequently, a complex interplay of histone modification and transcriptional activation leads to the induction of specific genes.
It is well known that the interplay of histone modification and DNA methylation affects the transcriptional regulation [ 25- 29].
DNA methylation is associated with histone modifications and the interplay of these epigenetic modifications is crucial to regulate the functioning of the genome by changing chromatin architecture.
Both positive (H3Ac; H3K4me2; H3K4me3; H3K9and H4Ac) anegative-actinging marks (H3K9me3; H3K27me3) are established across promoters during gene activation or gene repression, respectively, and the interplay of those histone modifications ultimately control gene expression [ 22].
One of the first examples for the interplay of different histone modifications was the observation that phosphorylation of S10 in H3 facilitated the acetylation of H3-K9 and K14, whereas methylation of H3-K9 inhibithe the phosphorylation of S10 (Rea et al., 2000), although later evidence indicated a possible coexistance of phosphorylated S10 and methylated K9 (Mateescu et al., 2004).
