Writing and Interpreting the Chromatin Enhancer Code in Myeloid Cells

H3Tail翻译后修饰的组合可以选择性地招募或排出蛋白质， 从而编码染色质编码的调节功能的功能结果-转录， 有丝分裂，DNA损伤修复，以及其他。例如，H3 S10和S28的磷酸化 已被证明是“启动”结合蛋白(HP1，和多梳代表复合体 成分，分别)相邻的甲基化赖氨酸取消了它们的抑制作用 活动。然而，乙酰化和乙酰化结合的流行率和功能相关性 这些相同残基和邻近的其他组蛋白尾部赖氨酸和丝氨酸的磷酸化(用于 例H4尾部S1和H4K5/K8/K12)不能很好地理解。使用量化的组合， 分析和生化方法，我们正在表征H3和H4尾巴的组合 赖氨酸乙酰化和丝氨酸磷酸化及其功能。我们正在追求一个假设，即 这些组合在基因激活和染色质紧凑和 通过重新招募或排出染色质结合因子来指定下游功能。对于功能型 评估这些染色质的特征，我们将重点放在胚胎干细胞上，这些组合 的修饰尤其丰富，并可能通过 细胞周期，以及巨噬细胞中这些组合基序在 炎性基因诱导。综上所述，近端组蛋白尾巴的组合效应 染色质效应蛋白上的乙酰化和磷酸化以及染色质状态被提出 是染色质编码功能的关键调控策略。

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.