of HDAC1D/Cn HDAC2 D/Dn neurospheres. PRKCd promoter hyperacetylation by HDAC2 is responsible for this defective phenotype in the brain.8 James Davie started his talk by describing a powerful chromatin fractionation method for chicken erythrocyte chromatin that had been previously elaborated in his lab. More recently, in combination with next generation DNA and RNA sequencing, it allowed them to define the organization of the chicken erythrocyte genome into chromosomal domains and obtain very useful information on the transcripts produced by these domains. In the second part of his talk, Dr. Davie focused on dynamic histone acetylation and RNA splicing. Histone deacetylases 1, 2), and serine/arginine-rich splicing factor 1 are involved in alternative splicing of the human myeloid cell leukemia sequence 1 gene. HDAC1/2 is recruited to MCL1 pre-mRNA by splicing factors and, together with KAT2B and other lysine acetyltransferases, catalyzes histone acetylation of MCL1 gene and directly regulates its splicing.9 Rafael Casellas discussed global chromatin acetylation and transcriptome amplification during lymphocyte activation. In G0, there are mechanisms–such as limiting RNA Polymerase II recruitment and activity–that maintain the transcriptome at basal levels. Subunits of transcription factor II human complex, including helicases involved in promoter melting, are generally downregulated in resting B cells, and promoters are polymerase-loaded but unmelted. In contrast, when the immune response takes place, there is an increase in histone acetylation, promoter melting, and transcription across the genome in activated B cells, which correlates with the enhancement observed in the expression of TFIIH and Myc.10 Maribel Parra outlined the role of HDAC7 in B lymphopoiesis. HDAC7 shows a lymphoid-specific expression pattern and is highly expressed in B lymphocytes, but not in myeloid cells such as macrophages. After reprogramming of pre-B cells intro macrophages by overexpression of C/EBPa, they found that HDAC7 shows a lymphoid-spedownregulated during the switch from pre-B cells to macrophages. However, reintroduction of HDAC7 causes derepression of myeloid genes in pre-B cells and abolishes crucial functions of macrophages by interacting with the transcription factor myocyte enhancer factor 2C. In conclusion, Dr. Parra reported a novel role for HDAC7 as a lymphoid-specific transcriptional repressor of inappropriate genes in pre-B cells, which is required for their trans-differentiation to macrophages.11 Histone Acetylation in Physiology and Disease John Denu opened the session by talking about the relationship between deacetylation activity of sirtuins and metabolism. Dr. Denu’s team has developed a quantitative mass spectrometry method to characterize the liver mitochondria acetyL-proteome during caloric restriction, in mice that lacked SIRT3. Applying this technique, they observed that SIRT3 regulates mitochondrial metabolism, especially under caloric restriction by deacetylating proteins involved in several pathways of DCC 2618 metabolism and mitochondrial maintenance.12 Furthermore, SIRT6 is a tumor suppressor that controls cancer metabolism. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19840865 In fact, SIRT6 KO mice show metabolic and degenerative phenotypes, and die by 4 weeks of age.13 Free fatty acids are able to stimulate SIRT6 deacetylation activity, and myristic acid inhibits SIRT6 dependent de-myristoylation. These results suggest that fatty acids liberated from a fasting diet are able to co