The Symer lab group: - We continued a comprehensive analysis of transcription of a candidate histone methyltransferase, Setdb2, in human, mouse and several other mammalian organisms tissues, revealing tissue-specific expression of alternatively spliced and chimeric transcripts. - We continued to identify and characterize in-frame and out-of-frame fusion transcripts linking Setdb2 to an adjacent independent gene, Phf11, which encodes a zinc finger-containing plant homeodomain motif. - We extended analysis of several protein-binding partners for the putative histone methyltransferases using yeast two hybrid screens;most of these binding partners now have been validated by co-immunoprecipitation experiments. Additional functional characterization of interactions between Setdb2 and the identified binding partners, which include an unannotated protein and other biologically interesting proteins, has been conducted. - We continued to characterize the partially penetrant phenotypes of a hypomorphic knockout mouse model lacking 70-80% of Setdb2 transcripts and probably most or all encoded proteins. Phenotypic characterization of these knockouts on various mouse strain backgrounds continued. Occasional homozygous hypomorphic mice developed an early myeloid lineage hyperproliferation, enlarged spleens, and/or dermatitis. - Specific antibodies against mouse and human Setdb2 have been developed and further characerized. We have expressed recombinant Setdb2 in baculovirus to facilitate characterization of its biochemical activities. - We extended findings that Setdb2 is an atypical histone methyltransferase, as it may also methylate other cellular proteins including HIV-1 Tat protein.
