MOLECULAR MECHANISM OF HISTONE ACETYLATION

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Eukaryotic DNA is packed in nucleosomal particles for assembly into high-order structures in the nucleus. Histone modifications in patterns mediated by numerous protein complexes are important for almost all DNA-related processes. Chromatin remodelling complexes can be grouped into two categories depending on nucleosomal conformational alteration or chromatin conformational alteration. Histone acetylation is responsible for chromatin conformational alteration, while Histone acetyltransferases (HATs) are the catalytic subunits of large multiprotein complexes that acetylate the N-terminal tail regions of histones to facilitate transcription activation in eukaryotes. Structural bases for histone modifications mediated by protein-protein complexes are critical to understand these processes. Although during past one decade, significant structural progresses are obtained to understand histone posttranslational modifications including acetylation, phosphorylation, methylation and ubiquitination [reviewed in 4], there are still a lot of unanswered questions: such as how many hotspots exist for modification within histone tails, how many different structural modules can recognize one single histone modification, how many different histone modification sites a single structural module can recognize, how many structural modules can be combined to recognize one single histone modification. In the long term, I would like to answer all these fundamental questions from the structural and molecular view by targeting several critical histone supercomplexes. At this proposal, I outline below a combination of structural and biochemical approaches to study protein-peptide recognition and protein-protein interaction events associated with Histone Code, such as Rtt109 complex mediated H3K56 acetylation and NuA4 complex mediated H4K16 acetylation