Writing and Interpreting the Chromatin Enhancer Code in Myeloid Cells

H3尾翻译后修饰的组合可以选择性地募集或排出蛋白质， 从而编码染色质编码的调节功能-转录的功能结果， 有丝分裂、DNA损伤修复等。例如，H3 S10和S28的磷酸化具有以下作用： 已被证明可以“启动”结合蛋白（HP 1和Polycomb抑制复合物 组分，EED，分别）的邻近甲基化赖氨酸废除其阻遏 活动然而，乙酰化和乙酰化结合的流行率和功能相关性是不确定的。 这些相同的残基和其它邻近的组蛋白尾部赖氨酸和丝氨酸的磷酸化（对于 示例H4尾S1和H4 K5/K8/K12）不太清楚。使用定量、 分析和生物化学方法，我们正在表征H3和H4尾的组合 赖氨酸乙酰化和丝氨酸磷酸化及其功能。我们在研究一个假设， 这些组合在基因活化和染色质致密化方面都具有显著特征， 通过募集或排出染色质结合因子来指定下游功能。用于功能 为了评估这些染色质特征，我们将重点放在胚胎干细胞上， 的修饰是特别丰富的，并可能在记忆中的活性基因，通过 细胞周期，也对巨噬细胞，其中这些组合基序是丰富的， 炎症基因诱导总之，近端组蛋白尾的组合的效果是显著的。 染色质效应蛋白和染色质状态上的乙酰化和磷酸化， 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.