About

Eric F. Joyce, Ph.D., is an Associate Professor of Genetics at the University of Pennsylvania's Perelman School of Medicine and a core member of the Epigenetics Institute. His research focuses on understanding how chromosomes are functionally organized and folded within the 3-D space of the nucleus, and how this organization is established and inherited across cell divisions. His lab aims to elucidate how dysfunctional chromosome organization contributes to genome instability, utilizing technologies to visualize chromosomes and subchromosomal regions at single-cell resolution and in high-throughput formats. The research employs both Drosophila and mammalian systems to explore the conservation and health-related implications of chromosome function mechanisms.

Research topics

• Biology
• Genetics
• Cell biology
• Computational biology
• Evolutionary biology

Selected publications

• A genetic screen for modifiers of cohesin clustering identifies regulators of genome folding

  Open MIND · 2026-01-01

  article

  The cohesin complex orchestrates 3D genome architecture through multiple steps including loading onto chromatin, DNA loop extrusion, stalling of extrusion, and unloading off chromatin. However, the upstream regulatory factors modulating these steps remain largely unexplored. Previous studies suggest that cohesin clustering correlates with its chromatin residence time and loop extrusion activity. Here, we developed, optimized, and performed an imaging-based genetic screen leveraging modulation of cohesin clustering to identify cohesin regulators. Using a sensitized background in which the cohesin unloader WAPL is partially degraded, we screened the druggable genome for effects on cohesin clustering. Through multiple rounds of screening and experimentation, we identified 7 enhancers and 10 suppressors of cohesin clustering. Several factors control genome folding at multiple loci and cohesin loading. Notably, our screen identified factors in mitochondrial function and epigenetic silencing, implicating these processes in the regulation of cohesin activity. This study offers a valuable resource identifying cohesin regulators and provides insights into upstream mechanisms governing genome folding.A large-scale imaging study identified factors involved in protein modification and gene regulation as genome folding regulators.

• The cytoskeleton contributes to abnormal genome–lamina interactions in <i>LMNA</i> -deficient cardiomyocytes

  The Journal of Cell Biology · 2026-03-27

  articleOpen access

  The spatial organization of chromatin at the nuclear lamina contributes to genome structure and gene regulation. Mechanical inputs are increasingly recognized as key regulators of nuclear architecture, and understanding how they control genome-lamina interactions and influence diseases associated with the nuclear lamina remains unclear. To understand the role of lamin proteins and the cytoskeleton in peripheral chromatin organization and consider this role in the context of laminopathies, we performed siRNA-mediated partial knockdown of lamin A/C (LMNA) in human cardiomyocytes and examined lamina-associated domains (LADs). Genome-wide mapping and locus-specific imaging reveal that LADs with a distinct molecular signature are preferentially vulnerable to LMNA reduction. A subset of these sensitive LADs retain lamina association when the linker of nucleoskeleton and cytoskeleton complex (LINC) is disrupted or microtubules are depolymerized. These findings indicate that, in the context of a compromised nuclear lamina, cytoskeletal inputs transmitted through the LINC complex play a key role in the reorganization of peripheral chromatin.

  PublisherOA PDFDOI

• Transcription and cohesin direct domain boundary spatial positioning and are linked to Friedreich’s ataxia

  Molecular Cell · 2026-05-01

  articleOpen access

  Variability in genome organization drives differential gene expression and shapes cellular diversity, yet whether transcription actively instructs genome structure and how this relationship is exploited in disease remains unclear. We show that transcription and cohesin direct the spatial positioning of lamina-associated domain (LAD) boundary genes. Transcriptional repression repositions LAD boundary genes to the nuclear lamina in a cohesin loop extrusion-dependent manner. Conversely, overactive cohesin is sufficient to reposition and silence LAD boundary genes, an effect counteracted by maintaining transcription. In Friedreich's ataxia, we demonstrate improper positioning of the pathogenically repressed LAD boundary gene FRATAXIN (FXN) at the nuclear periphery reflects an imbalance between transcription and cohesin dynamics. Importantly, modulating either transcription or cohesin activity restores FXN positioning and reactivates expression. Our findings establish transcription and cohesin as tunable molecular rheostats orchestrating LAD boundary spatial positioning and reveal how the flexible and dynamic nature of genome architecture is hijacked in disease.

  PublisherDOI

• A genetic screen for modifiers of cohesin clustering identifies regulators of genome folding

  UNC Libraries · 2026-02-06

  articleOpen access

  The cohesin complex orchestrates 3D genome architecture through multiple steps including loading onto chromatin, DNA loop extrusion, stalling of extrusion, and unloading off chromatin. However, the upstream regulatory factors modulating these steps remain largely unexplored. Previous studies suggest that cohesin clustering correlates with its chromatin residence time and loop extrusion activity. Here, we developed, optimized, and performed an imaging-based genetic screen leveraging modulation of cohesin clustering to identify cohesin regulators. Using a sensitized background in which the cohesin unloader WAPL is partially degraded, we screened the druggable genome for effects on cohesin clustering. Through multiple rounds of screening and experimentation, we identified 7 enhancers and 10 suppressors of cohesin clustering. Several factors control genome folding at multiple loci and cohesin loading. Notably, our screen identified factors in mitochondrial function and epigenetic silencing, implicating these processes in the regulation of cohesin activity. This study offers a valuable resource identifying cohesin regulators and provides insights into upstream mechanisms governing genome folding.A large-scale imaging study identified factors involved in protein modification and gene regulation as genome folding regulators.

  PublisherDOI

• A genetic screen for modifiers of cohesin clustering identifies regulators of genome folding

  Science Advances · 2026-01-30 · 2 citations

  articleOpen access

  The cohesin complex orchestrates 3D genome architecture through multiple steps including loading onto chromatin, DNA loop extrusion, stalling of extrusion, and unloading off chromatin. However, the upstream regulatory factors modulating these steps remain largely unexplored. Previous studies suggest that cohesin clustering correlates with its chromatin residence time and loop extrusion activity. Here, we developed, optimized, and performed an imaging-based genetic screen leveraging modulation of cohesin clustering to identify cohesin regulators. Using a sensitized background in which the cohesin unloader WAPL is partially degraded, we screened the druggable genome for effects on cohesin clustering. Through multiple rounds of screening and experimentation, we identified 7 enhancers and 10 suppressors of cohesin clustering. Several factors control genome folding at multiple loci and cohesin loading. Notably, our screen identified factors in mitochondrial function and epigenetic silencing, implicating these processes in the regulation of cohesin activity. This study offers a valuable resource identifying cohesin regulators and provides insights into upstream mechanisms governing genome folding.

  PublisherDOI

• B cell stimulation changes the structure and higher-order organization of the inactive X chromosome

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-02 · 1 citations

  preprintOpen access

  SUMMARY X Chromosome Inactivation (XCI) equalizes X-linked gene expression between sexes. B cells exhibit dynamic XCI, with Xist RNA/heterochromatic marks absent on the inactive X (Xi) in naive B cells but returning following mitogenic stimulation. The impact of dynamic XCI on Xi structure and maintenance was previously unknown. Here, we find dosage compensation of the Xi with state-specific XCI escape genes in naive and in vitro activated B cells. Allele-specific OligoPaints indicate similar Xi and Xa territories in B cells that are less compact than in fibroblasts. Allele-specific Hi-C reveals a lack of TAD-like structures on the Xi of naive B cells, and stimulation-induced alterations in TAD-like boundary strength independent of gene expression. Notably, Xist deletion in B cells changes TAD boundaries and large-scale Xi compaction. Altogether, our results uncover B cell-specific Xi plasticity which could underlie sex-biased biological mechanisms.

  PublisherOA PDFDOI

• CTCF/RAD21 organize the ground state of chromatin–nuclear speckle association

  Nature Structural & Molecular Biology · 2025-02-21 · 11 citations

  articleOpen access
  PublisherOA PDFDOI

• Nuclear speckles regulate functional programs in cancer

  Nature Cell Biology · 2025-01-02 · 17 citations

  articleOpen access
  PublisherOA PDFDOI

• Mechanistic and Epigenetic Partitioning of Lamina-Associated Chromatin Revealed by a Genome-Wide Imaging Screen

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-14 · 1 citations

  preprintOpen accessSenior authorCorresponding

  The nuclear periphery is a key site for heterochromatin organization in eukaryotic cells, where lamina-associated domains (LADs) promote transcriptional repression and genome stability. Despite their importance, the mechanisms governing LAD positioning in human cells remain poorly understood. To this end, we performed a genome-wide imaging-based siRNA screen and identified over 100 genes critical for perinuclear LAD localization, with a striking enrichment for RNA-binding proteins. Among these, hnRNPK emerged as a key regulator, required for the perinuclear positioning of approximately two-thirds of LADs genome-wide. Loss of hnRNPK led to LAD repositioning away from the nuclear periphery without altering their heterochromatin state, yet resulted in misexpression of genes within these domains. Notably, hnRNPK-sensitive LADs are uniquely marked by both H3K9me2 and H3K27me3, distinguishing them from hnRNPK-insensitive LADs that are enriched for H3K9me2 and H3K9me3. These findings reveal at least two mechanistically and epigenetically distinct LAD classes, suggesting that specialized pathways underlie their spatial organization. Our results uncover a pivotal role for hnRNPK in regulating the spatial organization of chromatin and highlight the broader diversity of LAD localization mechanisms.

  PublisherOA PDFDOI

• The length and strength of compartmental interactions are modulated by condensin II activity

  PLoS Genetics · 2025-07-01 · 2 citations

  articleOpen accessSenior author

  The spatial organization of the genome is crucial for its function and integrity. Although the ring-like SMC complex condensin II has a well-documented role in organizing mitotic chromosomes, its function in interphase chromatin structure has remained more enigmatic. Using a combination of Oligopaint fluorescence in situ hybridization (FISH) and Hi-C, we show that altering condensin II levels in diploid Drosophila cells significantly changes chromosome architecture at large length scales between chromatin compartments. Notably, condensin II overexpression disrupts the robust boundary between heterochromatin and euchromatin, leading to interactions that span entire chromosomes. These interactions occur independent from transcriptional changes, suggesting that the mechanisms driving compartment formation and their interactions might be distinct aspects of genome organization. Our results provide new insights into the dynamic nature of chromosome organization and underscore the importance of condensin II in maintaining genomic stability.

  PublisherDOI

Recent grants

• Regulation of chromatin folding in space and time

  NIH · $3.7M · 2018–2028

• Single-cell dissection of chromatin architecture mechanisms connecting pathologic instability and transcriptional silencing

  NIH · $3.1M · 2020–2025

• NIH Grant F32CA157188

  NIH · $155k · 2014

Frequent coauthors

• Son C. Nguyen

  University of Pennsylvania

  49 shared

• Jennifer M. Luppino

  University of Pennsylvania

  14 shared

• Kim S. McKim

  Rutgers Sexual and Reproductive Health and Rights

  14 shared

• Rajan Jain

  Philadelphia University

  12 shared

• Bryan R. Lajoie

  12 shared

• Liling Wan

  University of Pennsylvania

  11 shared

• Kaeli M. Mathias

  11 shared

• T. Niroshini Senaratne

  University of California, Los Angeles

  11 shared