About

Gregory Bowman is a professor in the Department of Biophysics at Johns Hopkins University. He received his undergraduate degree from the University of North Carolina at Chapel Hill and completed his Ph.D. at Princeton University, where he focused on X-ray crystallography, studying actin-binding proteins and an enterotoxin from rotavirus. His postdoctoral work at UC Berkeley in John Kuriyan's laboratory concentrated on structural biology, notably elucidating the structure of the pentameric RFC clamp loader bound to the trimeric PCNA sliding clamp, which suggested mechanisms of DNA-stimulated ATP hydrolysis and clamp release. Since joining the faculty at Johns Hopkins in 2005, Dr. Bowman’s research has centered on the structure and mechanisms of chromatin remodelers. His group investigates how these helicase-type motor proteins use ATP hydrolysis to actively reorganize nucleosomes, which are fundamental units of DNA packaging in many organisms, including humans. Disruptions in chromatin-regulating factors are linked to human diseases such as cancer. His work aims to understand how chromatin remodelers function and are regulated, with particular attention to the communication between their domains and their role in nucleosome positioning and DNA accessibility.

Research topics

• Cell biology
• Biology
• Genetics
• Chemistry
• Computational biology
• Biophysics
• Biochemistry

Selected publications

• BPS2026 – Uncovering the dynamics responsible for increased antibody affinity via MD simulations

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• A competitive regulatory mechanism of the Chd1 remodeler is integral to distorting nucleosomal DNA

  Nature Structural & Molecular Biology · 2025-05-28 · 4 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• BPS2025 - The Gq-specific inhibitor YM-254890 is an allosteric glue

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Androgens mediate sexual dimorphism in Pilarowski-Bjornsson Syndrome

  medRxiv · 2025-05-07 · 1 citations

  preprintOpen access

  Abstract Sex-specific penetrance in autosomal dominant Mendelian conditions is largely understudied. The neurodevelopmental disorder Pilarowski-Bjornsson syndrome (PILBOS) was initially described in females. Here, we describe the clinical and genetic characteristics of the largest PILBOS cohort to date, showing that both sexes can exhibit PILBOS features, although males are overrepresented. A mouse model carrying a human-derived Chd1 missense variant ( Chd1 R 616 Q /+ ) displays female-restricted phenotypes, including growth deficiency, anxiety and hypotonia. Orchiectomy unmasks a growth deficiency phenotype in male Chd1 R 616 Q /+ mice, while testosterone rescues the phenotype in females, implicating androgens in phenotype modulation. In the gnomAD and UK Biobank databases, rare missense variants in CHD1 are overrepresented in males, supporting a male protective effect. We identify 33 additional highly constrained autosomal genes with missense variant overrepresentation in males. Our results support androgen-regulated sexual dimorphism in PILBOS and open novel avenues to understand the mechanistic basis of sexual dimorphism in other autosomal Mendelian disorders. Graphical Abstract

  PublisherOA PDFDOI

• Native nucleosome-positioning elements as alternatives to the 601 sequence for nucleosome repositioning studies

  Nucleic Acids Research · 2025-09-05 · 4 citations

  articleOpen access

  Nucleosome repositioning is essential for establishing nucleosome-depleted regions to initiate transcription. This process has been extensively studied using structural, biochemical, and single-molecule approaches, which require homogeneously positioned nucleosomes. This is often achieved using the Widom 601 sequence, a highly efficient nucleosome-positioning element (NPE) selected for its unusually strong binding to the H3-H4 histone tetramer. Due to the artificial nature of 601, native NPEs are needed to explore the role of DNA sequence in nucleosome repositioning. Here, we characterize the position distributions and nucleosome formation free energies for a set of yeast native nucleosomes from Saccharomyces cerevisiae. We show these native NPEs can be used in biochemical studies of nucleosome repositioning by transcription factors (TFs) and the chromatin remodeler Chd1. TFs could directly reposition a fraction of nucleosomes containing native NPEs, but not 601-containing nucleosomes. In contrast, partial unwrapping was similar for 601 and native NPE sequences, and the rate of ATP-dependent remodeling by Chd1 was within the range of the fast and slow directions of the 601 nucleosomes. This set of native NPEs provides an alternative to the 601 NPE that can be used for probing the repositioning of nucleosomes that contain native DNA sequences.

  PublisherOA PDFDOI

• H3K56 acetylation regulates chromatin maturation following DNA replication

  Nature Communications · 2025-01-02 · 8 citations

  articleOpen access

  Following DNA replication, the newly reassembled chromatin is disorganized and must mature to its steady state to maintain both genome and epigenome integrity. However, the regulatory mechanisms governing this critical process remain poorly understood. Here, we show that histone H3K56 acetylation (H3K56ac), a mark on newly-synthesized H3, facilitates the remodeling of disorganized nucleosomes in nascent chromatin, and its removal at the subsequent G2/M phase of the cell cycle marks the completion of chromatin maturation. In vitro, H3K56ac enhances the activity of ISWI chromatin remodelers, including yeast ISW1 and its human equivalent SNF2h. In vivo, a deficiency of H3K56ac in nascent chromatin results in the formation of closely packed di-nucleosomes and/or tetra-nucleosomes. In contrast, abnormally high H3K56ac levels disrupt chromatin maturation, leading to genome instability. These findings establish a central role of H3K56ac in chromatin maturation and reveal a mechanism regulating this critical aspect of chromosome replication. Here, the authors show that histone H3 through H3K56 acetylation, is essential for chromatin remodelling in nascent chromatin post-DNA replication. Subsequent H3K56 deacetylation during G2/M signals chromatin maturation, ensures both genome and epigenome integrity.

  PublisherOA PDFDOI

• Mechanistic insights into INO80-type chromatin remodelers

  Current Opinion in Structural Biology · 2025-03-28 · 3 citations

  reviewOpen access1st authorCorresponding

  Chromatin remodelers are adenosine triphosphate (ATP)-driven enzymes that physically reorganize nucleosomes, the basic packaging unit of all eukaryotic chromosomes. INO80, SWR1/SRCAP, and TIP60 are large multisubunit remodelers that share similar components yet have distinct biochemical and biological functions. This review summarizes key architectural features of these complexes and how they engage DNA, nucleosomes, and hexasomes to carry out their tasks. • INO80-type remodelers share common subunits and architecture, yet have distinct functions. • INO80 binds to hexasomes and nucleosomes in different rotational phases, but in a topologically similar fashion. • SWR1/SRCAP flips nucleosomes to sequentially access each H2A/H2B dimer. • The Arp module is repurposed for each remodeler type.

  PublisherDOI

• GAGA zinc finger transcription factor searches chromatin by 1D–3D facilitated diffusion

  Nature Structural & Molecular Biology · 2025-08-05 · 11 citations

  articleOpen access

  The search for target sites on chromatin by eukaryotic sequence-specific transcription factors (TFs) is integral to the regulation of gene expression but the mechanism of nuclear exploration has remained obscure. Here we use multicolor single-molecule fluorescence resonance energy transfer and single-particle imaging to track the diffusion of purified Drosophila GAGA factor (GAF) on DNA and nucleosomes. Monomeric GAF DNA-binding domain (DBD) bearing one zinc finger finds its cognate site through one-dimensional (1D) or three-dimensional (3D) diffusion on bare DNA and rapidly slides back and forth between naturally clustered motifs for seconds before dissociation. Multimeric, full-length GAF also finds clustered motifs on DNA through 1D-3D diffusion but remains locked on target for longer periods. Nucleosome architecture effectively blocks GAF-DBD 1D sliding into the histone core but favors retention of GAF-DBD once it has bound to a solvent-exposed motif through 3D diffusion. Despite the occlusive nature of nucleosomes, 1D-3D facilitated diffusion enables GAF to effectively search for clustered cognate motifs in chromatin, providing a mechanism for navigation to nucleosomal and nucleosome-free sites by a member of the zinc finger TF family.

  PublisherOA PDFDOI

• BPS2025 - Extending the PopShift approach to protein small-molecule binding

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Native nucleosome-positioning elements for the investigation of nucleosome repositioning

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-19 · 2 citations

  preprintOpen access

  ABSTRACT Nucleosome repositioning is essential for establishing nucleosome-depleted regions (NDRs) to initiate transcription. This process has been extensively studied using structural, biochemical, and single-molecule approaches, which require homogenously positioned nucleosomes. This is often achieved using the Widom 601 sequence, a highly efficient nucleosome positioning element (NPE) selected for its unusually strong binding to the H3-H4 histone tetramer. Due to the artificial nature of 601, native NPEs are needed to explore the role of DNA sequence in nucleosome repositioning. Here, we characterize the position distributions and nucleosome formation free energy for a set of yeast native nucleosomes (YNNs) from Saccharomyces cerevisiae . We show these native NPEs can be used in biochemical studies of nucleosome repositioning by transcription factors (TFs) and the chromatin remodeler Chd1. TFs could directly reposition a fraction of nucleosomes containing native NPEs, but not 601-containing nucleosomes. In contrast, partial unwrapping was similar for 601 and native NPE sequences, and the rate of ATP-dependent remodeling by Chd1 was within the range of the fast and slow directions of the 601 nucleosomes. This set of native NPEs provides an alternative to the 601 NPE that can be used for probing the repositioning of nucleosomes that contain native DNA sequences.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R21CA181751

  NIH · $352k · 2016

• NIH Grant P41RR012408

  NIH · $17.2M · 2013

• Structural and Functional Characterization of the Chd1 Chromatin Remodeler

  NIH · $6.3M · 2008–2025

• NIH Grant F32GM066586

  NIH · $85k · 2004

Frequent coauthors

• Mike O’Donnell

  Rockefeller University

  38 shared

• John Kuriyan

  Vanderbilt University

  37 shared

• Steven L. Kazmirski

  Blueprint Medicines (United States)

  29 shared

• Ilana M. Nodelman

  Johns Hopkins University

  24 shared

• Eric R. Goedken

  AbbVie (United States)

  22 shared

• Robert F Levendosky

  Johns Hopkins University

  17 shared

• Yanxiang Zhao

  Hong Kong Polytechnic University

  16 shared

• Ashok Kumar Patel

  Indian Institute of Technology Delhi

  13 shared

Education

• PhD, Molecular Biology

  Princeton University