Brian D. Strahl

About

Professor Brian D. Strahl leads the Strahl lab at the University of North Carolina at Chapel Hill, within the School of Medicine. His research focuses on unraveling the fundamental mechanisms that drive chromatin biology, with a particular emphasis on understanding how histones, histone modifications, histone chaperones, and chromatin-remodeling enzymes precisely organize and control the genome. This regulation is essential for proper gene expression, cell growth and differentiation, development, and the ability to respond to environmental changes. The lab aims to define the mechanisms by which histones, their post-translational modifications (PTMs), and other chromatin-associated complexes contribute to human biology and disease. Histone modifications, whether acting alone or in combination, play crucial roles in gene transcription and heterochromatin formation, yet their exact contributions and how they contribute to human disease remain poorly understood. To address these unresolved questions, the Strahl lab employs Saccharomyces cerevisiae (yeast) and mammalian cell models, integrating genetic, biochemical, proteomic, and genomic methodologies. The research areas include defining how histone modifying enzymes and chaperones contribute to chromatin organization and gene transcription, uncovering the role of histone modifications and readers in metabolic gene transcription, and defining the rules by which chromatin regulators engage nucleosomes to regulate chromatin…

Research topics

• Genetics
• Biology
• Cell biology
• Computational biology
• Botany
• Nanotechnology
• Chemistry
• Physics
• Evolutionary biology
• Optics

Selected publications

• DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation

  Nature Communications · 2021 · 119 citations

  -H4K20me3 ensures heterochromatin targeting of DNMT1 and DNA methylation at LINE-1 retrotransposons, and cooperates with the previously reported readout of histone H3 tail modifications (i.e., H3K9me3 and H3 ubiquitylation) by the RFTS domain to allosterically regulate DNMT1's activity. Interplay between RFTS and BAH1 domains of DNMT1 profoundly impacts DNA methylation at both global and focal levels and genomic resistance to radiation-induced damage. Together, our study establishes a direct lin…

  DOI

• Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation

  Proceedings of the National Academy of Sciences · 2020 · 114 citations

  In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a spec…

  DOI

• Characterization of the plant homeodomain (PHD) reader family for their histone tail interactions

  Epigenetics & Chromatin · 2020 · 110 citations

  Senior authorCorresponding

  BACKGROUND: Plant homeodomain (PHD) fingers are central "readers" of histone post-translational modifications (PTMs) with > 100 PHD finger-containing proteins encoded by the human genome. Many of the PHDs studied to date bind to unmodified or methylated states of histone H3 lysine 4 (H3K4). Additionally, many of these domains, and the proteins they are contained in, have crucial roles in the regulation of gene expression and cancer development. Despite this, the majority of PHD fingers have gone…

  DOI

• An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability

  eLife · 2023 · 56 citations

  Senior authorCorresponding

  H3K4 methylation levels. Together, these observations reveal an acetylation 'chromatin switch' on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation.

  PublisherDOI

• Histone H3 proline 16 hydroxylation regulates mammalian gene expression

  Nature Genetics · 2022 · 47 citations

  DOI

Recent grants

• NIH Grant R01GM085394

  NIH · $1.2M · 2012

• Role of Dot1 and H3K79 methylation in gene regulation

  NSF · $750k · 2013–2016

• Chromatin maintenance in cancer progression

  NIH · $2.3M · 2015–2022

Frequent coauthors

• Scott B. Rothbart

  Van Andel Institute

  89 shared

• Krzysztof Krajewski

  69 shared

• Ian J. Davis

  University of North Carolina at Chapel Hill

  62 shared

• Tatiana G. Kutateladze

  University of Colorado Denver

  50 shared

• Raghuvar Dronamraju

  University of North Carolina at Chapel Hill

  42 shared

• Robert J. Duronio

  40 shared

• A. Gregory Matera

  University of North Carolina at Chapel Hill

  37 shared

• Stephen M. Fuchs

  Boston Children's Hospital

  31 shared

Education

• Ph.D., Molecular and Cell Biology

  University of California, San Francisco

  2004

• B.S., Molecular and Cell Biology

  University of California, Berkeley

  1999

Awards & honors

• UNC Excellence in Basic Science Mentoring Award (2019)
• UNC Oliver Smithies Investigator (2018)
• NIH Maximizing Investigators' Research Award (MIRA) (2018)
• Philip & Ruth Hettleman Prize (2009)
• NIH Exceptional, Unconventional Research Enabling Knowledge…

Similar researchers at University of North Carolina at Chapel Hill

• Michael Rubinsteinh-90
• Ronald Swanstromh-83
• William Marzluffh-78