We initially made two deletion forms of SRSF1 that lack C-terminal residues in the RS domain

unpublished. Ed Seto elaborated on the importance of increasing the knowledge on HDACs substrates, due to the interdependent relationship that exists between them and the search for optimal HDAC inhibitors. HDACi are potential anti-cancer drugs that are able to cause cell cycle arrest, revert cell transformation, and restrain tumor growth in animals. Dr. Seto’s team performed an analysis of potential Sirtuin1 substrates using proteomics techniques such as stable isotope labeling of amino acids in cell culture. The study identified the human PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19835880 ortholog of Drosophila melanogaster male absent on the first, hMOF, which is a Volume 10 Issue 5 446 Epigenetics MYST family histone H4 lysine 16-specific acetyltransferase, as a SIRT1 substrate. Deacetylation of hMOF by SIRT1 inhibits its HAT activity. This promotes protein ubiquitination and inhibits hMOF-mediated apoptosis and DNA repair EMA-401 web activity in response to DNA damage through the acetylation of p53 at lysine 120.2 Acetylation, Chromatin Structure, and Gene Expression Tony Kouzarides shared with the audience the research from his lab that focuses on the identification of new small molecule inhibitors against HATs and HDACs for the treatment of cancer. He also talked about the pathways involved in the generation of newly discovered histone PTMs and the potential targeting of these PTMs for cancer therapies. Dr. Kouzarides presented bromodomain and extra terminal inhibitor, an inhibitor of bromodomaincontaining proteins, as a potentially effective drug for the treatment of mixed lineage leukemia -fusion leukemia,3 which is currently in clinical trials. With regards to the novel histone methylation pathways, he talked about the glutamine methylation of histone H2A by fibrillarin, which constitutes a RNA Polymerase I dedicated modification.4 He also described the citrullination of arginine in histone H1, which is mediated by the enzyme peptidyl arginine de-iminase, type IV. PADI4 is expressed in neutrophils and in stem cells, where it mediates the de-condensation of chromatin and appears to be overexpressed in malignant tumors. Finally, he reported on a yet unpublished novel histone methylation pathway that participates in DNA replication and involves H3K36me1 and H3K37me1, which are enriched at yeast DNA replication origins. Both PTMs are required for the synergistic binding of minichromosome maintenance complex component 2 to H3. Whereas K37me1 reduces this binding, K36me1 increases it. They searched for the enzymes that mediate this process and found that suppressor of position effect variegation enhancer of Zeste and trithorax 4 deletion reduced H3K36me1 at DNA replication origins and delayed S-phase, while overexpression of SET4 induced cell proliferation. In human cells, MLL5 is a homolog of SET4 and its knockdown reduces cell proliferation and induces cell cycle arrest at G1, providing a potential target for new MLL inhibitors. Jerry Workman talked about histone acetyltransferase complexes. The general control of amino acid synthesis 5 subunit of SptAdaGcn5 acetyltransferase chromatinmodifying complex is responsible for sucrose non-fermenting acetylation. Snf2 acetylation, within switch of the mating type chromatin remodeling complex, reduces the binding of this complex to acetylated nucleosomes and affects Swi/ Snf complex genome wide occupancy.5 Besides, HATs regulate the genomic dynamics of chromatin remodelers through acetylation of histones, acetylation of remodelers, and a possible com