BIOLOGICAL & PHYSICAL CHEMISTRY
B.Sc., University of Wisconsin – Stevens Point, 2000
Ph.D., University of Minnesota, 2005
American Cancer Society Postdoctoral Fellow, The Scripps Research Institute, 2007-2010
Phone: (801) 581-3186
Office: 1493 GH
Activities & Awards
- Sigma Chi Fraternity Outstanding Faculty Award, 2016
- Extraordinary Faculty Achievement Recognition Award, 2016
- Career Services Faculty Recognition Award, 2016
- American Cancer Society Research Scholar Grant, 2014
- American Cancer Society Postdoctoral Fellowship, 2007
The primary focus of our research is to utilize a multidisciplinary approach incorporating structural biology, biophysics, biochemistry, molecular biology and cellular biology to investigate mechanistic questions in the area of transcriptional regulation. We are particularly interested in applying these methodologies to discern structure-function relationships for specialized transcription factors that recognize epigenetically modified methyl-CpG DNA sequences.
In eukaryotes, DNA methylation in the context of CpG dinucleotides is an essential epigenetic modification required for genomic stability, regulation of chromatin structure and long-term transcriptional silencing of genes. Aberrant alterations in genomic DNA methylation patterns, leading to inappropriate gene silencing, have been associated with cancer promotion and progression. These findings have prompted an interest in discerning the regulatory mechanisms of DNA methylation in gene transcription by investigating the factors that are involved in modification, recognition, and translation of the methylation signal. Methyl-CpG binding proteins directly read and interpret the methylation signal, making them ideal reporters for the methylation status in the cancerous state.
Initial areas of research interest include: 1) identification and characterization of specific methyl-CpG binding protein DNA targets utilizing a parallel in vitro biophysical and in cell genomic approach to delineate the molecular mechanisms by which these proteins recognize DNA and regulate transcription in cancer; 2) structural investigations of these DNA interactions to ascertain differential modes of recognition between various methyl-CpG binding proteins; and 3) structural and biophysical characterizations of protein/protein interactions to begin evaluating how interpretation of the methylation signal triggers chromatin remodeling. Structural evaluation of methyl-CpG binding proteins with their interaction partners is critical for gaining mechanistic insight into the complex roles of these proteins in cancer epigenetics. Further, as important interpreters of methylation status in the cancerous state, methyl-CpG binding protein binding activities can be exploited for identifying cancer-specific methylated genes that may have diagnostic value. Thus, this combined research approach may provide the means for identifying epigenetic-based biomarkers as well as establish the basis for advancing therapeutic design directed toward key methyl-CpG binding protein regulatory networks/pathways.
- Pozner, A., Hudson, N. O., Trewhella, J., Terooatea, T. W., Miller, S. A., Buck-Koehntop, B. A. The C-terminal Zinc Fingers of ZBTB38 are Novel Selective Readers of DNA Methylation, J. Mol. Biol., 2017, (https://doi.org/10.1016/j.jmb.2017.12.014).
- Pozner, A.; Terooatea, T. W.; Buck-Koehntop, B. A. Cell Specific Kaiso (ZBTB33) Regulation of Cell Cycle Through cyclin D1 and cyclin E1, J. Biol. Chem., 2016, 291 (47), 24538-24550.
- Terooatea, T. W.; Pozner, A.; Buck-Koehntop, B. A. PAtCh-Cap: input strategy for improving analysis of ChIP-exo data sets and beyond.Nucleic Acids Res., 2016, 44 (21), e159.
- Buck-Koehntop, B. A.; Defossez, P.-A. On how Mammalian Transcription Factors Recognize Methylated DNA. Epigenetics2013, 8, 131-137
Buck-Koehntop, B. A.; Stanfield, R. L.; Ekiert, D. C.; Martinez-Yamout, M. A.; Dyson, H. J.; Wilson, I. A.; Wright, P. E. Molecular Basis for Recognition of Methylated and Specific DNA Sequences by the Zinc Finger Protein Kaiso. Proc. Nat. Acad. Sci.2012, 109, 15229-15234.
Buck-Koehntop, B. A.; Martinez-Yamout, M. A.; Dyson, H. J.; Wright, P. E. Kaiso uses all Three Zinc Fingers and Adjacent Sequence Motifs for High Affinity Binding to Sequence-specific and Methyl-CpG DNA Targets. FEBS Lett.2012, 586, 734-739.