Biology subjects

VonHandorf, A.

Publications and source records attributed to VonHandorf, A..

4 recordsLinked to original sources

bioRxiv2026

Memory T cell rapid recall is driven by memory-specific AP-1 recruitment determined by epigenome and co-factor interactions

CD4 T cell memory is essential for long-lasting protective immunity to repeat infections. Unlike naive T cells, memory cells possess rapid recall ability to quickly produce effector molecules in response to antigen re-exposure. This ability was shown to be associated with epigenetic gene poising. Here, we examine how the activation-inducible transcription factors, AP{square}1 and NF{square}{kappa}B, regulate rapid recall gene expression. We found that AP-1 is required for their induction and that the enhanced induction of rapid recall genes in memory cells is associated with memory-specific binding of AP{square}1. Memory-specific AP{square}1 binding, in turn, is enabled by enhanced chromatin accessibility and reduced DNA methylation at regulatory elements. As the AP-1 DNA-binding motif itself does not contain methylatable CpGs, methylation likely affects the binding of AP-1 co-factors, such as ETS proteins, or accessibility of the region in general. Finally, both common and memory-specific AP{square}1/NF{square}{kappa}B binding sites show strong overlap with autoimmune and inflammatory disease risk variants, highlighting the clinical relevance of memory T cell epigenetic regulation.

immunology↗

bioRxiv2025

Systematic investigation of Epstein-Barr virus transcriptional regulator interactions with the human genome

We systematically investigate interactions between Epstein-Barr virus (EBV) transcriptional regulators (vTRs) and the human genome. Starting with 16 known and candidate vTRs, we identify nine whose introduction into human cells results in substantial alterations to host gene expression. Genome-scale determination of vTR genomic binding events and alterations to chromatin accessibility reveals a detailed map of EBVs functional interactions with the human genome, including >100,000 vTR binding events impacting almost a quarter of all human genes. BMRF1 emerges as a potent regulator, impacting >7,000 genes and altering >37,000 chromatin regions. Our results provide new evidence that EBV RTA interacts with and stabilizes the binding of human RBPJ. Network analysis reveals that many human genes are targeted by multiple EBV vTRs, highlighting the vast coordinated impact of EBV on human gene expression. This study provides a valuable, extensive resource for examining EBV-induced alterations to human gene regulation, with data available on multiple platforms.

genomics↗

bioRxiv2024

Human cytomegalovirus extensively re-organizes the human genome, diminishing TEAD1 transcription factor activity

Human cytomegalovirus (HCMV) infects up to 80% of the worlds population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hours after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity. We confirm extensive concordant loss of TEAD1 binding, active H3K27ac histone marks, and chromatin looping interactions upon infection. Our data position TEAD1 at the top of a hierarchy involving multiple altered important developmental pathways. HCMV infection reduces TEAD1 activity through four distinct mechanisms: closing of TEAD1-bound chromatin, reduction of YAP1 and phosphorylated YAP1 levels, reduction of TEAD1 transcript and protein levels, and alteration of TEAD1 exon-6 usage. Altered TEAD1-based mechanisms are highly enriched at genetic risk loci associated with eye and ear development, providing mechanistic insight into HCMVs established roles in these processes.

genomics↗

bioRxiv2023

Lineage tracing of newly accrued nuclei in skeletal myofibers uncovers distinct transcripts and interplay between nuclear populations

Multinucleated skeletal muscle cells have an obligatory need to acquire additional nuclei through fusion with activated skeletal muscle stem cells when responding to both developmental and adaptive growth stimuli. A fundamental question in skeletal muscle biology has been the reason underlying this need for new nuclei in syncytial cells that already harbor hundreds of nuclei. To begin to answer this long-standing question, we utilized nuclear RNA-sequencing approaches and developed a lineage tracing strategy capable of defining the transcriptional state of recently fused nuclei and distinguishing this state from that of pre-existing nuclei. Our findings reveal the presence of conserved markers of newly fused nuclei both during development and after a hypertrophic stimulus in the adult. However, newly fused nuclei also exhibit divergent gene expression that is determined by the myogenic environment to which they fuse. Moreover, accrual of new nuclei through fusion is required for nuclei already resident in adult myofibers to mount a normal transcriptional response to a load-inducing stimulus. We propose a model of mutual regulation in the control of skeletal muscle development and adaptations, where newly fused and pre-existing myonuclear populations influence each other to maintain optimal functional growth.

cell biology↗