Signaling Network Model of Chromatin Stuart L. Schreiber, Bradley E. Bernstein  Cell  Volume 111, Issue 6, Pages 771-778 (December 2002) DOI: 10.1016/S0092-8674(02)01196-0

Figure 1 Schematic Depicting Representative RTK and Histone Protein Domain Organizations Both proteins comprise core domains flanked by unfolded regions rich in posttranslationally modified residues. Cell 2002 111, 771-778DOI: (10.1016/S0092-8674(02)01196-0)

Figure 2 RTK- and Histone-Mediated Signal Transduction Mechanisms Are Analogous Signal transduction at the cell membrane is initiated by PDGF-induced receptor dimerization, leading to transphosphorylation of tyrosines in the kinase insert. Signal transduction in the nucleus is initiated by a HAT that acetylates lysines in the H3 tail. In both cases, the signal is relayed by recruitment of enzymatic activity to newly formed docking sites. As illustrative examples, at the membrane, phosphatidylinositol-3,4,5-triphosphate (PIP3) is generated, locally activating Akt; in the nucleus, nucleosomes are remodeled, locally facilitating transcription. Cell 2002 111, 771-778DOI: (10.1016/S0092-8674(02)01196-0)

Figure 3 Signal Transducing Modifications in PDGFR and Histone H4 Are Redundant As demonstrated in systematic profiling studies of IEG induction, the multiple tyrosines in the RTK insert are redundant (Fambrough et al., 1999). Similarly, lysine residues in the H4 tail that are subject to acetylation are redundant, at least with respect to induction of GAL1 (Durrin et al., 1991). In both cases, rather than specifying unique downstream function, multiple, modifiable residues appear to ensure transduction of a robust signal (see text). Cell 2002 111, 771-778DOI: (10.1016/S0092-8674(02)01196-0)

Figure 4 Feedback Mechanisms in Chromatin A classic example of feedback in signal transduction is the processivity of Src kinases. The Src SH2 domain has affinity for the phosphorylated product of its kinase domain. As depicted in (A), this results in positive feedback, which promotes switch-like behavior in RTK signaling. Positive feedback in chromatin signaling is mediated by enzymes that contain chromodomains (B) and bromodomains (C). Double-negative feedback, which also promotes switch-like behavior and robustness in a network, is observed in the interplay between Lys9 methylation and Ser10 phosphorylation of histone H3 (D). For discussion of the relevance of Figures 4B and 4C to epigenetic inheritance, see text. (E) TDAC is unique among deacetylases in that it has two deacetylase domains. One of these domains may be used for binding, resulting in either negative or positive feedback. Cell 2002 111, 771-778DOI: (10.1016/S0092-8674(02)01196-0)