the more complex transcriptional regulation required by these sessile organisms. HDACs appear to be deriving from an ancestral acetyl-binding domain, as HDAC homologs have been found in bacteria in the form of Acetoin utilization proteins (AcuC) proteins. Subcellular distribution Within the Class I HDACs, HDAC 1, 2, and 3 are found primarily in the nucleus, whereas HDAC8 is found in both the nucleus and the cytoplasm, and is also membrane-associated. Class II HDACs (HDAC4, 5, 6, 7 9, and 10) are able to shuttle in and out of the nucleus, depending on different signals. HDAC6 is a cytoplasmic, microtubule-associated enzyme. HDAC6 deacetylates tubulin, Hsp90, and cortactin, and forms complexes with other partner proteins, and is, therefore, involved in a variety of biological processes. Function Histone modification Histone tails are normally positively charged due to amine groups present on their lysine and arginine amino acids. These positive charges help the histone tails to interact with and bind to the negatively charged phosphate groups on the DNA backbone. Acetylation, which occurs normally in a cell, neutralizes the positive charges on the histone by changing amines into amides and decreases the ability of the histones to bind to DNA. This decreased binding allows chromatin expansion, permitting genetic transcription to take place. Histone deacetylases remove those acetyl groups, increasing the positive charge of histone tails and encouraging high-affinity binding between the histones and DNA backbone. The increased DNA binding condenses DNA structure, preventing transcription. Histone deacetylase is involved in a series of pathways within the living system. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), these are: Environmental information processing; signal transduction; notch signaling pathway PATH:ko04330 Cellular processes; cell growth and death; cell cycle PATH:ko04110 Human diseases; cancers; chronic myeloid leukemia PATH:ko05220 Histone acetylation plays an important role in the regulation of gene expression. Hyperacetylated chromatin is transcriptionally active, and hypoacetylated chromatin is silent. A study on mice found that a specific subset of mouse genes (7%) was deregulated in the absence of HDAC1. Their study also found a regulatory crosstalk between HDAC1 and HDAC2 and suggest a novel function for HDAC1 as a transcriptional coactivator. HDAC1 expression was found to be increased in the prefrontal cortex of schizophrenia subjects, negatively correlating with the expression of GAD67 mRNA. Histone modification in neurons Neurons are electrically excitable cells within the nervous system and are organized together in circuits. In hippocampal neurons in culture,