Martha L. Bulyk
Division of Genetics, Brigham & Women's Hospital
Transcription factors and DNA regulatory elements.
Although numerous genomes have been sequenced, much still remains to be understood about how gene expression is regulated. The interactions between transcription factors (TFs) and their DNA binding sites are an integral part of the regulatory networks within cells. We employ combined experimental and computational strategies in studying these regulatory interactions to discover cis regulatory codes in eukaryotic genomes.
We have developed high-throughput experimental technologies that allow rapid, high-throughput characterization of the DNA binding sequence specificities of both TFs and synthetically designed proteins. We use data on TF DNA binding to identify TFs that act together to co-regulate gene expression. We are also examining the effects of protein partners and DNA shape on TF function. We are combining sequence, evolutionary, structural, and PBM data to understand the molecular determinants of protein-DNA binding specificity and its evolution, and to investigate the effects of mutations and naturally occurring genetic variation on human TFs. We are interested in understanding the quantitative nature of information encoded within transcriptional enhancers. We develop novel technologies and computational approaches for a better understanding of the cis regulatory element function, mechanisms in transcriptional regulation by TFs, and their evolution.
Gisselbrecht SS, Barrera LA, Porsch M, Aboukhalil A, Estep PW 3rd, Vedenko A, Palagi A, Kim Y, Zhu X, Busser BW, Gamble CE, Iagovitina A, Singhania A, Michelson AM, Bulyk ML. Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos. Nature Methods (2013) 10(8):774-80.
*Nakagawa S, *Gisselbrecht SS, *Rogers JM, †Hartl DL, †Bulyk ML. DNA binding specificity changes in the evolution of forkhead transcription factors. Proc. Natl. Acad. Sci. USA (2013) 110(30):12349-54.
†Siggers T, Reddy J, Barron B, †Bulyk ML. Diversification of transcription factor paralogs via noncanonical modularity in C2H2 zinc finger DNA binding. Molecular Cell (2014) 55(4):640-8.
Barrera LA, Vedenko A, Kurland JV, Rogers JM, Gisselbrecht SS, Rossin EJ, Woodard J, Mariani L, Kock KH, Inukai S, Siggers T, Shokri L, Gordân R, Sahni N, Cotsapas C, Hao T, Yi S, Kellis M, Daly MJ, Vidal M, Hill DE, Bulyk ML. Survey of variation in human transcription factors reveals prevalent DNA binding changes. Science. 2016 Mar 25;351(6280):1450-1454. doi: 10.1126/science.aad2257. Epub 2016 Mar 24.
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