Robert J. Duronio
· Cary C. Boshamer Professor & Department ChairVerifiedUniversity of North Carolina at Chapel Hill · Biology
Active 1989–2026
About
Robert J. Duronio is the Cary C. Boshamer Professor and Department Chair in the Department of Genetics at the University of North Carolina at Chapel Hill. His research focuses on understanding the molecular mechanisms that regulate DNA replication and cell proliferation during animal development. He studies the cell cycle, which consists of phases G1, S, G2, and M, and how gene expression events control the decision of cells to enter S phase and proliferate or to exit the cycle and differentiate. His work emphasizes the importance of cell cycle regulation in coordinating tissue development and function, as well as its breakdown in the formation of cancer. Duronio's research utilizes the fruit fly Drosophila melanogaster as a model organism because the genes controlling cell proliferation are highly conserved across species, including humans. This allows for the application of genetic and cell biological techniques to study gene function in a whole animal context. His studies aim to elucidate how cell cycle regulatory pathways operate normally and how their malfunction contributes to cancer, with the goal of gaining insights into the molecular basis of deregulated growth in human disease.
Research topics
- Biology
- Genetics
- Cell biology
Selected publications
bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-04
articleOpen accessSenior authorCorrespondingAbstract Coupling histone gene expression to S phase of the cell cycle is essential for genome duplication and stability. Activation of Cyclin E/Cdk2 at the G1-S transition stimulates high-level expression of histone genes during S phase, but how histone genes are turned off at the end of S phase is not understood. Here we demonstrate that the essential Drosophila gene mute functions to repress inappropriate histone mRNA accumulation outside of S phase by counteracting Cyclin E/Cdk2-dependent phosphorylation of Mxc, which activates histone gene expression. Additionally, Mute plays contrasting roles in histone gene expression during S phase by promoting high levels of H1 , H2a and H2b expression but not H3 and H4 . Although Mute is present only at replication-dependent histone genes, its loss leads to 801 differentially regulated genes, primarily those involved in muscle related processes in late-stage embryos. Thus, disruptions of histone gene expression control alters the transcriptome resulting in developmental defects.
Histone H3 availability is more important for development than H3.2 versus H3.3 subtype identity
bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-10
articleOpen accessCorrespondingABSTRACT The distinct contributions of replication-dependent and replication-independent histones to development and genome function remain unclear. In this study, we investigate how the distinct protein identities of the histone H3.2 and H3.3 subtypes contribute to development and gene regulation in Drosophila . Comparing animals in which the replication-independent H3.3 genes were mutated to produce the replication-dependent H3.2 protein with those carrying deletions of the replication-independent H3.3 genes revealed that replication-independent H3.3 is essential for fertility, adult locomotor behavior, and normal longevity. However, development to adulthood does not depend on which replication-independent H3 subtype is expressed from the H3.3 loci. Moreover, replication-independent H3.3 is not required to establish or maintain global patterns of chromatin accessibility or gene expression in the adult brain. Surprisingly, we find that expression of H3.2 from the replication-dependent HisC locus is essential in post-replicative cells in the absence of replication-independent H3.3, and we uncover a critical role for the HIRA histone chaperone complex in preserving genome function when replication-independent H3.3 is deleted. We conclude that an available pool of H3 is more critical than the specific identity of H3 in the pool.
UNC Libraries · 2025-06-07
articleOpen access1st authorCorrespondingMolecular Biology of the Cell · 2025-05-21 · 4 citations
articleSenior authorCoordinated expression of replication-dependent (RD) histones genes occurs within the Histone Locus Body (HLB) during S-phase, but the molecular steps in transcription that are cell-cycle regulated are unknown. We report that Drosophila RNA Pol II promotes HLB formation and is enriched in the HLB outside of S-phase, including G 1 -arrested cells that do not transcribe RD histone genes. In contrast, the transcription elongation factor Spt6 is enriched in HLBs only during S-phase. Proliferating cells in the wing and eye primordium express full-length histone mRNAs during S-phase but express only short nascent transcripts in cells in G 1 or G 2 consistent with these transcripts being paused and then terminated. Full-length transcripts are produced when Cyclin E/Cdk2 is activated as cells enter S-phase. Thus, activation of transcription elongation by Cyclin E/Cdk2 and not recruitment of RNA pol II to the HLB is the critical step that links histone gene expression to cell-cycle progression.
UNC Libraries · 2025-05-20
articleOpen accessTight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the on/off state of cell identity genes such as the Hox factors. Polycomb group complexes repress target genes, whereas trithorax group complexes are required for their expression. Although trithorax and its orthologs function as methyltransferases specific to histone H3 lysine 4 (H3K4), there is no direct evidence that H3K4 regulates Polycomb group target genes in vivo. Using histone gene replacement in <em>Drosophila</em>, we provide evidence of two key roles for replication-dependent histone H3.2K4 in Polycomb target gene control. First, we found that H3.2K4 mutants mimic H3.2K4me3 in antagonizing methyltransferase activity of the PRC2 Polycomb group complex. Second, we found that H3.2K4 is also required for proper activation of Polycomb targets. We conclude that H3.2K4 directly regulates Polycomb target gene expression.
UNC Libraries · 2025-07-23
articleOpen accessMutating replication-dependent (RD) histone genes is an important tool for understanding chromatin-based epigenetic regulation. Deploying this tool in metazoans is particularly challenging because RD histones in these organisms are typically encoded by many genes, often located at multiple loci. Such gene arrangements make the ability to generate homogenous histone mutant genotypes by site-specific gene editing quite difficult. Drosophila melanogaster provides a solution to this problem because the RD histone genes are organized into a single large tandem array that can be deleted and replaced with transgenes containing mutant histone genes. In the last ∼15 years several different RD histone gene replacement platforms were developed using this simple strategy. However, each platform contains weaknesses that preclude full use of the powerful developmental genetic capabilities available to Drosophila researchers. Here we describe the development of a newly engineered platform that rectifies many of these weaknesses. We used CRISPR to precisely delete the RD histone gene array (HisC), replacing it with a multifunctional cassette that permits site-specific insertion of either one or two synthetic gene arrays using selectable markers. We designed this cassette with the ability to selectively delete each of the integrated gene arrays in specific tissues using site-specific recombinases. We also present a method for rapidly synthesizing histone gene arrays of any genotype using Golden Gate cloning technologies. These improvements facilitate generation of histone mutant cells in various tissues at different stages of Drosophila development and provide an opportunity to apply forward genetic strategies to interrogate chromatin structure and gene regulation.
2025-03-31
peer-reviewSenior authorUNC Libraries · 2024-09-14 · 1 citations
articleOpen accessMonomethylation of lysine 20 of histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects of genome function that are mediated by H4K20me binding proteins. We interrogated this model in a developing animal by comparing in parallel the transcriptomes of Set8 null, H4 K20R/A, and l(3)mbt mutant Drosophila melanogaster. We found that the gene expression profiles of H4 K20A and H4 K20R larvae are markedly different than Set8 null larvae despite similar reductions in H4K20me1. Set8 null mutant cells have a severely disrupted transcriptome and fail to proliferate in vivo, but these phenotypes are not recapitulated by mutation of H4 K20, indicating that the developmental defects of Set8 null animals are largely due to H4K20me1-independent effects on gene expression. Furthermore, the H4K20me1 binding protein L(3)mbt is recruited to the transcription start sites of most genes independently of H4K20me even though genes bound by L(3)mbt have high levels of H4K20me1. Moreover, both Set8 and L(3)mbt bind to purified H4K20R nucleosomes in vitro. We conclude that gene expression changes in Set8 null and H4 K20 mutants cannot be explained by loss of H4K20me1 or L(3)mbt binding to chromatin and therefore that H4K20me1 does not play a large role in gene expression.
UNC Libraries · 2024-06-15
articleOpen access1st authorCorrespondingHistone locus bodies (HLBs) are biomolecular condensates that assemble at replication-dependent (RD) histone genes in animal cells. These genes produce unique mRNAs that are not polyadenylated and instead end in a conserved 3' stem loop critical for coordinated production of histone proteins during S phase of the cell cycle. Several evolutionarily conserved factors necessary for synthesis of RD histone mRNAs concentrate only in the HLB. Moreover, because HLBs are present throughout the cell cycle even though RD histone genes are only expressed during S phase, changes in HLB composition during cell cycle progression drive much of the cell cycle regulation of RD histone gene expression. Thus, HLBs provide a powerful opportunity to determine the cause-and-effect relationships between nuclear body formation and cell cycle regulated gene expression. In this review, we focus on progress during the last five years that has advanced our understanding of HLB biology.
Genetics · 2024-07-22 · 9 citations
articleOpen accessSenior authorMutating replication-dependent (RD) histone genes is an important tool for understanding chromatin-based epigenetic regulation. Deploying this tool in metazoans is particularly challenging because RD histones in these organisms are typically encoded by many genes, often located at multiple loci. Such gene arrangements make the ability to generate homogenous histone mutant genotypes by site-specific gene editing quite difficult. Drosophila melanogaster provides a solution to this problem because the RD histone genes are organized into a single large tandem array that can be deleted and replaced with transgenes containing mutant histone genes. In the last ∼15 years several different RD histone gene replacement platforms were developed using this simple strategy. However, each platform contains weaknesses that preclude full use of the powerful developmental genetic capabilities available to Drosophila researchers. Here we describe the development of a newly engineered platform that rectifies many of these weaknesses. We used CRISPR to precisely delete the RD histone gene array (HisC), replacing it with a multifunctional cassette that permits site-specific insertion of either one or two synthetic gene arrays using selectable markers. We designed this cassette with the ability to selectively delete each of the integrated gene arrays in specific tissues using site-specific recombinases. We also present a method for rapidly synthesizing histone gene arrays of any genotype using Golden Gate cloning technologies. These improvements facilitate the generation of histone mutant cells in various tissues at different stages of Drosophila development and provide an opportunity to apply forward genetic strategies to interrogate chromatin structure and gene regulation.
Recent grants
Regulation of Histone Gene Expression During Drosophila Development
NSF · $455k · 2004–2008
Epigenetic Control of the Cell Cycle During Animal Development
NIH · $1.7M · 2022–2027
Histone mRNA Regulation in Development
NIH · $11.9M · 2024–2025
Regulation of Metazoan DNA Replication by Chromatin
NIH · $1.2M · 2018–2022
Engineering histone genes to interrogate the epigenetic code in space and time
NIH · $2.2M · 2013–2018
Frequent coauthors
- 104 shared
William F. Marzluff
University of North Carolina at Chapel Hill
- 68 shared
A. Gregory Matera
University of North Carolina at Chapel Hill
- 51 shared
Daniel J. McKay
University of North Carolina at Chapel Hill
- 40 shared
Brian D. Strahl
University of North Carolina at Chapel Hill
- 30 shared
Jeffrey I. Gordon
Washington University in St. Louis
- 23 shared
Robin L. Armstrong
University of North Carolina at Chapel Hill
- 20 shared
Harmony R. Salzler
University of North Carolina at Chapel Hill
- 20 shared
Pamela Y. Malek
University of North Carolina at Chapel Hill
Education
- 1996
Postdoctoral Fellow, Biochemistry & Biophysics
UCSF Medical Center
- 1991
PhD, Biochemistry and Molecular Biology
Washington University in Saint Louis
- 1986
B.S., Biology
Massachusetts Institute of Technology
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