Assistant Professor of Chemistry
B.S. University of Wisconsin, Stevens Point
Ph.D. University of Minnesota, Twin Cities
Bethany Buck-Koehntop's Lab Page
Bethany Buck-Koehntop's PubMed Literature Search
Biological Chemistry Program
Molecular Biology Program
Structural Biology and Cancer Epigenetics
The primary focus of our research is to utilize a multidisciplinary approach incorporating structural biology, biophysics, biochemistry, molecular biology and cellular biology to explore structure-function relationships in protein/protein and protein/nucleic acid interactions. We are particularly interested in applying these methodologies to investigate specialized transcription factors termed methyl-CpG DNA binding proteins that specifically recognize methylated DNA sequences.
In mammals, DNA methylation is the primary mode of long-term transcriptional gene silencing in normal cells. Profound alterations in genomic DNA methylation patterns have also been associated with abnormal proliferation of cells preceding cancer development. 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 interpret the methylation signal leading to chromatin remodeling and gene silencing. To date, we know very little about the complex mechanisms by which these events occur.
Initial areas of interest include: 1) identifying specific DNA targets for methyl-CpG binding proteins utilizing a combination of in vitro and in cell methodologies; 2) structural investigation of these DNA interactions to ascertain differential modes of DNA recognition; and 3) structural characterization 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 providing atomic-resolution detail of binding interfaces and gaining mechanistic insight into the complex roles of these proteins in cancer epigenetics. Further, we believe that methyl-CpG binding proteins represent important interpreters of methylation status in the cancerous state that can be exploited to find disease specific biomarkers for diagnosis and prognosis. Thus, this combined research approach is critical for identification of new epigenetic-based cancer diagnostics and advancing the rational design of therapeutics for the prevention and treatment of cancer.
- Pozner A, Terooatea TW, Buck-Koehntop BA (2016) Cell Specific Kaiso (ZBTB33) Regulation of Cell Cycle Through cyclin D1 and cyclin E1,J Biol Chem, 291(47):24538-24550
- Terooatea TW, Pozner A, Buck-Koehntop BA (2016) PAtCh-Cap: input strategy for improving analysis of ChIP-exo data sets and beyond. Nucleic Acids Res, 44(21):e159
- Buck-Koehntop BA, Defossez, P-A (2013) On How Mammalian Transcription Factors Recognize Methylated DNA. Epigenetics, 8(2):131-137
- Buck-Koehntop BA, Stanfield RL, Ekiert DC, Martinez-Yamout MA, Dyson HJ, Wilson IA, Wright PE (2012) Molecular Basis for Recognition of Methylated and Specific DNA Sequences by the Zinc Finger Kaiso. Proc Nat Acad Sci USA, 109(38):15229-15234
- Buck-Koehntop BA, Martinez-Yamout MA, Dyson HJ, Wright PE (2012) Kaiso uses all Three Zinc Fingers and Adjacent Sequence Motifs for High Affinity Binding to Sequence-specific and Methyl-CpG DNA Targets. FEBS Lett, 586:734-739