A5007965740- Genomics and Chromatin Dynamics
- Chromatin Remodeling and Cancer
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- Chromosomal and Genetic Variations
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Molecular Biology Techniques and Applications
- RNA Interference and Gene Delivery
- Bacterial Genetics and Biotechnology
- Gene expression and cancer classification
- Histone Deacetylase Inhibitors Research
- Electron Spin Resonance Studies
- Genomics and Phylogenetic Studies
- Mechanisms of cancer metastasis
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Antibiotic Resistance in Bacteria
University of Dundee
2015-2024
Wellcome Trust
2002-2014
University of St Andrews
2009
University of California, San Francisco
2008
Constructor University
2005
Pennsylvania State University
1994-2003
Université Laval
1998
Jichi Medical University
1998
Howard Hughes Medical Institute
1998
University of Oxford
1990-1995
The transcriptional adaptor protein Gcn5 has been identified as a nuclear histone acetyltransferase (HAT). Although recombinant yeast efficiently acetylates free histones, it fails to acetylate histones contained in nucleosomes, indicating that additional components are required for acetylation of chromosomal histones. We report here functions catalytic subunit two high-molecular-mass native HAT complexes, with apparent molecular masses 0.8 and 1.8 megadalton (MD), respectively, which...
RNA-seq is now the technology of choice for genome-wide differential gene expression experiments, but it not clear how many biological replicates are needed to ensure valid interpretation results or which statistical tools best analyzing data. An experiment with 48 in each two conditions was performed answer these questions and provide guidelines experimental design. With three replicates, nine 11 evaluated found only 20%-40% significantly differentially expressed (SDE) genes identified full...
The transcription initiation factor TFIID is a multimeric protein complex composed of TATA box–binding (TBP) and many TBP-associated factors (TAFIIs). TAFIIs are important cofactors that mediate activated by providing interaction sites for distinct activators. Here, we present evidence human TAFII250 its homologs in Drosophila yeast have histone acetyltransferase (HAT) activity vitro. HAT maps to the central, most conserved portion dTAFII230 yTAFII130. resembles GCN5 it specific histones H3...
Posttranslational modifications play key roles in regulating chromatin plasticity. Although various chromatin-remodeling enzymes have been described that respond to specific histone modifications, little is known about the role of poly[adenosine 5'-diphosphate (ADP)-ribose] remodeling. Here, we identify a enzyme, ALC1 (Amplified Liver Cancer 1, also as CHD1L), interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding. Our results define DNA damage-response protein...
Lysine acetylation of histones defines the epigenetic status human embryonic stem cells and orchestrates DNA replication, chromosome condensation, transcription, telomeric silencing, repair. A detailed mechanistic explanation these phenomena is impeded by limited availability homogeneously acetylated histones. We report a general method for production site-specifically recombinant genetically encoding acetyl-lysine. reconstitute histone octamers, nucleosomes, nucleosomal arrays bearing...
The positioning of nucleosomes within the coding regions eukaryotic genes is aligned with respect to transcriptional start sites. This organization likely influence many genetic processes, requiring access underlying DNA. Here, we show that combined action Isw1 and Chd1 nucleosome-spacing enzymes required maintain this organization. In absence these enzymes, regular majority lost. Exceptions include region upstream promoter, +1 nucleosome, a subset locations distributed throughout where...
The SWI/SNF complex participates in the restructuring of chromatin for transcription. function yeast remodeling a nucleosome array has now been analyzed vitro. Binding purified to disrupted multiple nucleosomes an adenosine triphosphate-dependent reaction. However, removal left deoxyribonuclease I-hypersensitive site specifically at that was bound by derivatives transcription factor Gal4p. Analysis individual revealed catalyzed eviction histones from Gal4-bound nucleosomes. Thus, transient...
ISWI proteins form the catalytic core of a subset ATP-dependent chromatin remodeling activities in eukaryotes from yeast to man. Many these complexes have been found reposition nucleosomes but with different directionalities. We find that Isw1a, Isw2, and Chd1 enzymes preferentially move toward more central locations on short DNA fragments whereas Isw1b does not. Importantly, inherent positioning properties play an important role determining where are relocated by all enzymes. However, key...
Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. However, our understanding how histone directly affect chromatin function remains limited. In this study, we investigate acetylation H3 at lysine 64 (H3K64ac), previously uncharacterized on the lateral surface octamer. We show that H3K64ac regulates nucleosome stability and facilitates eviction hence expression in vivo. line with this, demonstrate is enriched vivo transcriptional...
Within the genomes of metazoans, nucleosomes are highly organised adjacent to binding sites for a subset transcription factors. Here we have sought investigate which chromatin remodelling enzymes responsible this. We find that ATP-dependent enzyme SNF2H plays major role organising arrays architectural factor CTCF and acts promote binding. At many other related SNF2L contribute nucleosome organisation. The action at is functionally important as depletion or affects common group genes. This...