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 to investigate the DNA binding properties of sequence-specific 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 biochemical 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 investigating pioneer factors to understand how sequence or chromatin features may influence the pioneer binding to nucleosomes. We are also investigating the potential differences in regulatory functions of alternative transcript isoforms of TFs, focusing on those differentially expressed in breast cancer. We are interested in understanding the quantitative nature of information encoded within transcriptional enhancers and silencers. 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.

Selected Publications:

Gisselbrecht SS, Palagi A, Kurland JV, Rogers JM, Ozadam H, Zhan Y, Dekker J, Bulyk ML. Transcriptional Silencers in Drosophila Serve a Dual Role as Transcriptional Enhancers in Alternate Cellular Contexts. Molecular Cell. 2020 Jan 16;77(2):324-337.

Mariani L*, Weinand K*, Gisselbrecht SS, Bulyk ML. MEDEA: analysis of transcription factor binding motifs in accessible chromatin. Genome Research, 2020. 30(5), 736-748. Epub 2020 May 18.

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

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.