We study a transcription factor called the polyomavirus enhancer binding protein 2/core-binding factor (CBF). CBF is comprised of two subunits, one which binds DNA directly (CBFa), and a second subunit (CBFß) which associates with the a subunit. CBF binds sites in the enhancers of all four T cell receptor chain genes, the IL-3 promoter, myeloperoxidase promoter, and the enhancers of many mammalian retroviruses.

Four genes encode subunits of CBF. Two genes are disrupted by chromosomal translocations or inversions in leukemias in humans. The CBFa subunit encoded by the acute myeloid leukemia 1 (AML1) gene is disrupted by the t(8;21) associated with acute myeloid leukemia of the M2 subtype. The CBFb subunit gene is disrupted by the inv(16) associated with acute myeloid leukemia M4 eosinophil subtype. Together t(8;21) and inv(16) are associated with >11% of acute myeloid leukemias in humans. Currently, we are studying the biochemical properties of CBF, the role of CBF in T cell and myeloid cell differentiation, and the contribution of CBF to retroviral pathogenesis.

Huang, X., J.W. Peng, N.A. Speck, and J.H. Bushweller. Core binding factor b revealed: solution structure and map of the CBFa binding site. Nature Structural Biology, 6, 624-627, 1999.

Berardi, M., C. Sun, M. Zehr, F. Agildgard, J. Peng, N.A. Speck, and J.H. Bushweller Berardi, M., C. Sun, M. Zehr, F. Agildgard, J. Peng, N.A. Speck, and J.H. Bushweller. The Ig fold of the core binding factor a Runt domain is a member of a family of structurally and functionally related Ig fold DNA binding domains. Structure, 7, 1247-1256, 1999.

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