BBS Faculty Member - Martha Bulyk

Martha Bulyk

Division of Genetics, Department of Medicine; Department of Pathology
Associate Member of The Broad Institute of MIT and Harvard

Harvard Medical School
NRB, Room 466D
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-525-4725
Fax: 617-525-4705
Email: mlbulyk@genetics.med.harvard.edu
Lab Members: 5 postdocs, 3 grad students, 3 technicians
Visit my lab page here.



Although numerous eukaryotic genomes have been sequenced, much still remains to be understood about how the genes in those genomes are regulated. The interactions between transcription factors (TFs) and their DNA binding sites are an integral part of the regulatory networks within cells. We employ numerous combined experimental and computational strategies in studying these regulatory interactions, to discover cis regulatory codes in the genome.

To permit a genome-wide scan of all possible TF binding sites in a given genome, we developed universal protein binding microarrays (PBMs), a DNA microarray-based technology that allows rapid, high-throughput characterization of the DNA binding site sequence specificities of proteins. We are using PBMs to study hundreds of TFs in
Drosophila and mammals, so that we may predict sets of co-regulatory TFs acting together at candidate transcriptional cis regulatory modules, such as transcriptional enhancers. We are examining the effects of protein-protein interactions in DNA binding. We are also investigating divergence within TF families and how different members of a TF family gain distinct regulatory roles. We are investigating the effects of mutations and naturally occurring genetic variation on human TFs. We are combining sequence, evolutionary, structural, and PBM data to understand the molecular determinants of protein-DNA binding specificity and its evolution. We have developed computational strategies that employ comparative genomics methods for prediction of tissue-specific transcriptional enhancers in fly, and separately in mammals. Many of these predicted enhancers recently have been validated in vivo. In our analyses, we infer each TF’s relative importance for a given cell-type-specific gene expression pattern. We are interested in understanding the quantitative nature of information encoded within transcriptional enhancers, as it pertains to spatiotemporal specificity of enhancer activity. Technology development projects include novel approaches for high-throughput, experimental identification of tissue/cell-type-specific enhancers. The results of these experiments and analyses aim for a better understanding of the functions, locations and organization of DNA regulatory elements, and their evolution.



Last Update: 9/12/2019



Publications

For a complete listing of publications click here.

 


 

References: (*co-1st authors; †co-corresponding authors):

Rogers JM, Waters CT, Seegar TCM, Jarrett SM, Hallworth AN, Blacklow SC, Bulyk ML. Bispecific Forkhead transcription factor FoxN3 recognizes two distinct motifs with different DNA shapes. Molecular Cell. 2019 Apr 18; 74(2):245-253.e6

Mariani L, Weinand K, Vedenko A, Barrera LA, Bulyk ML. Identification of human lineage-specific transcriptional co-regulators enabled by a glossary of binding modules and tunable genomic backgrounds. Cell Systems. 2017 Sep 27;5(3):187–201

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):774-780.

*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

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) 351(6280):1450-1454. (*co-2nd authors)



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