Michael Atchison

..We show for the first time that YY1 plays a novel role in CSR and controls nuclear AID protein levels...

..Disruption of these functions may causally initiate cancer or may contribute to disease progression. Targeting YY1 functions provides possible avenues for clinical intervention...

..Finally, students must be made aware of career options after graduation...

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..Finally, we found that YY1, as well as Polycomb, required the co-repressor protein CtBP for repression in vivo. These results provide a mechanism for recruitment of vertebrate PcG complexes to DNA and demonstrate new functions for YY1...

..These results reveal a new role for CtBP in controlling YY1 DNA binding and recruitment of PcG proteins to DNA...

..Therefore, YY1 was transiently required for correction of fly defects and was dispensable past the pharate adult stage. Possible mechanisms of repression by YY1 are discussed...

..Our results show a novel mechanism of protein factor switching in transcription regulation of the cytochrome c oxidase Vb gene during myogenesis...

..Our results support a model in which CtBP regulates expression of intergenic transcripts that controls DNA binding by PcG proteins and subsequent histone modifications and transcriptional activity...

..We propose that this motif be named the REPO domain for its function in recruitment of Polycomb. The REPO domain is well conserved in YY1 orthologs and in related proteins...

..1 and possibly other members of the Ets family of oncoproteins subverts normal cellular differentiation in part by inhibiting the acetylation of critical nuclear factors involved in balancing cellular proliferation and maturation...

..When the Drosophila homolog of Yaf2 (dRYBP) is mutated, PcG recruitment to DNA is reduced. Taken together, our results suggest that Yaf2 serves as a molecular bridge between YY1 and other PcG complex proteins...

..Our data demonstrate that some Myc target cells are bipotent B-lymphoid/myeloid progenitors with the astonishing capacity to undergo successive rounds of lineage switching...

..However, a Pip dominant negative mutant inhibited germ line I micro transcripts. The importance of these results for late B-cell functions is discussed...

..Using chromatin immunoprecipitation assays we found that TSA caused preferential acetylation of histone H3 at the 3' enhancer. The relevance of these studies for PU.1 function in transcription and hemopoietic development is discussed...

..This analysis demonstrates kappa activation is a multistep process initiated in early B cell precursors before Igmu recombination and finalized only after the pre-B cell stage...

..The anticipated results will have relevant applicability to stem cell and germline biology and lead to a better understanding of human reproduction. ..

..PcG proteins are also implicated in muscle differentiation. Therefore, we will test the roles of YY1, CtBP, SUMO-1, and PCNA in differentation of myblasts into myotubes. ..

..Students also participate in a school-wide research day held each Spring. Future goals include further expansion of funded slots and development of additional strategies for recruitment of veterinary students into research careers. ..

..The unique perspectives offered by veterinarian-scientists are likely to promote innovation in diagnosis and treatment, and to stimulate the development of multidisciplinary research teams consistent with the goals of the NIH Roadmap. ..

..Understanding these processes therefore directly relates to public health. ..

..These studies may provide new mechanisms for enhancing the success of bone marrow transplantation treatments, and may provide new targets for diseases caused by PcG proteins or stem cell dysfunction. ..

..These studies represent parallel in vitro and in vivo approaches to study gene regulation and cellular differentiation. ..

..Our long-term goals are to determine whether the factors that control kappaE3' enhancer activity also play a role in B cell differentiation...

..Finally, we will pursue studies relating to position- independent and copy number-dependent transcription of transfected Ig kappa genes...

..Many of the proteins that bind to the 3 prime enhancer are encoded by proto-oncogenes. Therefore, these studies will also be useful for understanding the roles of these proteins in oncogenesis. ..

..PcG proteins are also implicated in muscle differentiation. Therefore, we will test the roles of YY1, CtBP, SUMO-1, and PCNA in differentation of myblasts into myotubes. ..