Our Research Areas
At the Strahl lab, we are unraveling the fundamental mechanisms that drive chromatin biology. We aim to understand how histones, histone modifications, histone chaperones, and chromatin-remodeling enzymes precisely organize and control the genome. This regulation is essential for proper cell fate decision-making, cell growth, development, and environmental response. The malfunction of chromatin proteins and enzymes is linked to numerous human diseases, notably cancer.
research area 1
Decoding the Role
of Histone Modifications in Chromatin Organization
How do histone-modifying enzymes and chaperones contribute to chromatin organization and gene transcription? Poorly understood are the details by which histone chaperones and histone modifications orchestrate gene transcription events. We have made key contributions to answering questions in this area by defining how histone-modifying enzymes, e.g., Set1, Set2, Rpd3S, Bre1-Rad6, and the Spt6-Spn1 histone chaperone, function in chromatin-based gene transcription. We are continuing to investigate these and other transcription factors and remodelers to explain how they regulate nucleosome disassembly/reassembly and maintain the fidelity of gene transcription.
research area 2
Uncovering the Mechanisms
of Gene Transcription Through Histone PTMs
How do novel histone modifications and readers direct gene transcription? New histone modification types (e.g., crotonylation) and histone reader modules (e.g., YEATS domains) have been discovered, but their functions are largely unknown. We have made significant advances in this area by determining how the YEATS domain-containing Taf14, and its reading of histone crotonylation, represses metabolic genes during the yeast metabolic cycle (YMC). The YMC represents an unprecedented opportunity to define how metabolic flux and a dynamically changing chromatin environment precisely control oscillating gene transcription programs required for cell survival. Some of our current studies are focused on the precise molecular mechanism of Taf14’s control of transcription. In addition, we are examining the functions of other YEATS-containing chromatin regulators and other recently described reader domains such as the ZZ domain.
research area 3
Uncovering the Mechanisms
of Gene Transcription Through Histone PTMs
What are the rules by which histone readers engage nucleosomes and how do these interactions regulate downstream events in chromatin? Despite considerable information regarding reader domain-histone modification interactions, there is a substantial gap concerning how chromatin-associated proteins recognize these modifications in the context of nucleosomes and how “paired” domains interpret the Histone Code. We are defining the binding preferences of reader domains and how these proteins achieve multivalent interactions in chromatin that dictate their functions. Defining these binding events has significant implication for diseases caused by dysregulated histone modification. Some examples include defining the combinatorial readout of histones by UHRF1 that promotes DNMT1-directeed DNA methylation maintenance, Rpd3S that prevents spurious transcription during gene transcription, and PBRM1 of the PBAF remodeling complex to control gene transcription. Other multi-domain chromatin reader modules are currently under investigation.
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Additional collaborative projects
The Strahl lab is also collaborating with a variety of labs at UNC and beyond to understand chromatin regulation and epigenetics.
