The present invention is directed to novel nucleic acids that encode novel HDAC proteins, which have an affect on chromatin structure and transcription. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods of producing the polypeptides of the present invention. Further provided by the present invention are methods of identifying novel compositions which mediate HDAC8 and the use of such compositions in diagnosis and treatment of disease.