Michael Joseph Buck
University at Buffalo, NY·Genetics
Every cell carries the same DNA, yet different cells switch on different genes. The first step is a transcription factor (TF), a protein that reads a short DNA sequence and helps turn nearby genes on.
- Fields
Genetics
Biochemistry
Biology
- Topics
transcription factors
pioneer factors
nucleosome
- Grants
- 1 known grant, through Aug 2029
What they work on
- Determine how transcription factors recognize binding sites wrapped on a nucleosome, the DNA spool unit, using the in vitro Pioneer-seq assay to compare sites at every nucleosome position and across sequence variants.
- Test how histone modifications and nucleosome positioning change pioneer factor binding by running Pioneer-seq with modified histones and different nucleosome DNA sequences.
- Identify the chromatin features, chromatin remodelers and partner factors that pioneer factors need to bind in cells by expressing them in well-characterized cell lines, including disease models.
- Build quantitative models that predict how proteins bind their DNA targets within or near nucleosomes, combining test-tube and in-cell binding data.
More about the research
But DNA in cells is tightly packed around protein spools called nucleosomes, and many binding sites are hidden. Even pioneer factors, special TFs that can reach packed DNA, do not bind all their targets. This project aims to work out the rules that decide when a TF can bind DNA inside packed chromatin.
Why it matters
TF binding is the first step in switching genes on, so knowing its rules could explain how genes are controlled in normal development and how this goes wrong in disease. Quantitative models of binding in packed chromatin could eventually help researchers predict, and possibly steer, gene activity in development and disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Motoki Takaku
University of North Dakota, ND·Genetics
Identify the nucleosome positions and shapes that let the pioneer factor GATA3 open chromatin and drive the mesenchymal-to-epithelial transition in triple-negative breast cancer cells, using high-resolution nucleosome mapping.
Chris Hsiung
University of California-San Francisco, CA·Genetics·Early-career
Build CRISPR/Cas-based tools that can deliver many combinations of chromatin signals at once, overcoming the limited combinatorial capacity of existing systems for manipulating gene regulation in human cells.
Shinya Watanabe
University of Massachusetts Chan Medical School, MA·Biochemistry
Define the roles of brain- and heart-specific DPF1 and DPF3 in the cBAF remodeling complex by rebuilding cBAF with DPF1, DPF2, DPF3 or no DPF protein and comparing nucleosome binding, sliding and ATPase activity.
The school
University at Buffalo: 32 labs on PI Pages, $542M a year on research, 316 research doctorates a year.
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