权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Writing and Interpreting the Chromatin Enhancer Code in Myeloid Cells

写入和解释骨髓细胞中的染色质增强子代码

基本信息

批准号：
8686006
负责人：
Steven Zvi Josefowicz
金额：
$ 5.51万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8686006
关键词：
Acetylation Address Affect Binding Binding Proteins Biochemical Biological Assay Bromodomain Cell Cycle Cell Cycle Kinetics Cell Cycle Stage Cell Separation Cells Chromatin Code Collaborations Complex DNA DNA Repair Docking Early Gene Transcriptions Enhancers Evaluation Event Gene Activation Gene Expression Regulation Genes Genetic Transcription Genomics Histones Immediate-Early Genes Immunofluorescence Microscopy Immunoprecipitation In Vitro Inflammation Inflammatory Interphase K-18 conjugate Kinetics Leukocytes Link Location Lysine Maps Memory Mitosis Mitotic Modification Mutagenesis Myeloid Cells N-terminal Neighborhoods Neurons Normal Cell Nuclear Outcome Pattern Peptides Phosphorylation Physical condensation Polycomb Post-Translational Protein Processing Prevalence Proteins Reading Recruitment Activity Regulation Resolution Role SECTM1 gene Serine Site Specific qualifier value Tail Techniques Transcription Elongation Transcription Process Transcriptional Activation Work Writing cell type cellular development chromatin immunoprecipitation chromatin protein combinatorial density embryonic stem cell functional gain gene induction histone acetyltransferase histone modification insight macrophage neoplastic cell novel novel strategies response

项目摘要

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.

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，