
A7 - Prof. Dr. Ann Ehrenhofer-Murray
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A7: Acetylation of lysine 16 on histone H4 as a dynamic epigenetic mark during transcription and replication
Chromatin packaging of DNA ensures proper compaction and organization of the genetic material in the eukaryotic nucleus, but at the same time restricts its accessibility to DNA regulatory processes. One principle way of altering chromatin function is by posttranslational modification of the histones that make up the nucleosomes. One such modification, the acetylation of lysine 16 of histone H4 (H4 K16Ac) by the SAS-I histone acetyltransferase complex, will be the focus of this study, because it conveys special properties to chromatin in that it inhibits heterochromatin formation by altering the compaction of the chromatin fibre and by counteracting the binding of the repressive silent information regulator (SIR) complex in yeast.
Here, we will study the dynamics of H4 K16Ac deposition by SAS-I within and outside of S-phase, and we will study how this depends on histone chaperones. As a complementary view, we will perform biochemical experiments towards the structural analysis of the SAS-I complex and will combine this with functional analysis in vivo of structure- and homology-informed mutants in order to obtain molecular insights into SAS-I function. Altogether, this will allow us to uncover the basic principles of epigenetic inheritance within the functional module of H4 K16 acetylation.
Project-Related Publications
- Authors:Heise F, Chung HR, Weber JM, Xu Z, Klein-Hitpass L, Steinmetz LM, Vingron M, Ehrenhofer-Murray AE.
Journal:Nucleic Acids Res Year:2012; Volume:40Issue:(1):Pages:65-74.
Title:Genome-wide H4 K16 acetylation by SAS-I is deposited independently of transcription and histone exchange - Authors:Meijsing SH, Ehrenhofer-Murray AE
Journal:Genes Dev Year:2001; Volume:15Issue:(23):Pages:3169-82.
Title:The silencing complex SAS-I links histone acetylation to the assembly of repressed chroma-tin by CAF-I and Asf1 in Saccharomyces cerevisiae - Authors:Ehrentraut S, Weber JM, Dybowski JN, Hoffmann D, Ehrenhofer-Murray AE
Journal:Proc Natl Acad Sci U S A Year:2010; Volume:107Issue:(12):Pages:5522-7.
Title:Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate - Authors:Schaper S, Franke J, Meijsing SH, Ehrenhofer-Murray AE
Journal:J Cell Sci Year:2005; Volume:118Issue:(Pt 7):Pages:1473-84.
Title:Nuclear import of the histone acetyltransferase complex SAS-I in Saccharomyces cere-visiae