Writing and Interpreting the Chromatin Enhancer Code in Myeloid Cells

H3尾部翻译后修饰的组合可以选择性地招募或排出蛋白质，

Combinations of H3 tail post-translational modifications can selectively recruit or eject proteins, thus encoding functional consequences for chromatin encoded regulatory functions-transcription, mitosis, DNA damage repair, and others. For example, phosphorylation of H3 S10 and S28 have been demonstrated to "kick off" binding proteins (HP1, and Polycomb Represive Complex component, EED, respectively) of the neighboring methylated lysine abrogating their repressive activities. However, the prevalence and functional relevance of the combination of acetylation and phosphorylation of these same residues and other neighboring histone tail lysines and serines (for example H4 tail S1 and H4K5/K8/K12) is not well understood. Using a combination of quantitative, analytical, and biochemical approaches, we are characterizing the combinations of H3 and H4 tail lysine acetylations and serine phosphorylations and their function. We are pursuing a hypothesis that these combinations feature prominently in both gene activation and chromatin compaction and specify downstream function by recruiting or ejecting chromatin binding factors. For functional evaluation of these chromatin features, we focus on embryonic stem cells where these combinations of modifications are especially abundant and may function in memory of active genes through the cell cycle, and also on macrophages in which these combinatorial motifs are enriched during inflammatory gene induction. In summary, the effects of combinations of proximal histone tail acetylation and phosphorylation on chromatin effector proteins and chromatin state are proposed to be a critical regulatory strategy for chromatin-encoded function.