Philipp Voigt

We are interested in understanding the molecular mechanisms that control the accurate and timely expression of genes during development.

Post-translational modifications to histone proteins play key roles in these processes. We aim to understand how histone modifications or ‘marks’ set up chromatin states that support active transcription or gene repression. In particular, we are interested in the so-called bivalent domains, a peculiar combination of active and repressive histone marks found at developmentally regulated genes.

Bivalent domains are thought to keep genes in a poised state in undifferentiated cells such as embryonic stem cells, ready for activation upon signals that cause the cells to differentiate. We study how different histone modifiers and readers interact to establish complex regulatory systems that control development and cause disease if mis-regulated. We are taking a multidisciplinary approach to tackle these questions, combining biochemistry with proteomic, genomic, cell-biological, imaging-based, and systems biology-inspired techniques.

Understanding exactly how these complex regulatory systems establish proper gene expression patterns during development will allow us to investigate how these systems deteriorate during ageing and cause disease, while opening avenues towards mitigating such processes and towards applications in regenerative medicine.

Latest Publications

H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation.
Dong J, LeBlanc C, Poulet A, Mermaz B, Villarino G, Webb KM, Joly V, Mendez J, Voigt P, Jacob Y

Epigenetic mechanisms play diverse roles in the regulation of genome stability in eukaryotes. In Arabidopsis thaliana, genome stability is maintained during DNA replication by the H3.1K27 methyltransferases ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) and ATXR6, which catalyze the deposition of K27me1 on replication-dependent H3.1 variants. The loss of H3.1K27me1 in atxr5 atxr6 double mutants leads to heterochromatin defects, including transcriptional de-repression and genomic instability, but the molecular mechanisms involved remain largely unknown. In this study, we identified the transcriptional co-activator and conserved histone acetyltransferase GCN5 as a mediator of transcriptional de-repression and genomic instability in the absence of H3.1K27me1. GCN5 is part of a SAGA-like complex in plants that requires the GCN5-interacting protein ADA2b and the chromatin remodeler CHR6 to mediate the heterochromatic defects in atxr5 atxr6 mutants. Our results also indicate that Arabidopsis GCN5 acetylates multiple lysine residues on H3.1 variants, but H3.1K27 and H3.1K36 play essential functions in inducing genomic instability in the absence of H3.1K27me1. Finally, we show that H3.1K36 acetylation by GCN5 is negatively regulated by H3.1K27me1 in vitro. Overall, this work reveals a key molecular role for H3.1K27me1 in maintaining transcriptional silencing and genome stability in heterochromatin by restricting GCN5-mediated histone acetylation in plants.

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The Plant cell, 33, 4, 31 05 2021

PMID: 33793815

The 3' processing of antisense RNAs physically links to chromatin-based transcriptional control.
Fang X, Wu Z, Raitskin O, Webb K, Voigt P, Lu T, Howard M, Dean C

Noncoding RNA plays essential roles in transcriptional control and chromatin silencing. At antisense transcription quantitatively influences transcriptional output, but the mechanism by which this occurs is still unclear. Proximal polyadenylation of the antisense transcripts by FCA, an RNA-binding protein that physically interacts with RNA 3' processing factors, reduces transcription. This process genetically requires FLD, a homolog of the H3K4 demethylase LSD1. However, the mechanism linking RNA processing to FLD function had not been established. Here, we show that FLD tightly associates with LUMINIDEPENDENS (LD) and SET DOMAIN GROUP 26 (SDG26) in vivo, and, together, they prevent accumulation of monomethylated H3K4 (H3K4me1) over the gene body. SDG26 interacts with the RNA 3' processing factor FY (WDR33), thus linking activities for proximal polyadenylation of the antisense transcripts to FLD/LD/SDG26-associated H3K4 demethylation. We propose this demethylation antagonizes an active transcription module, thus reducing H3K36me3 accumulation and increasing H3K27me3. Consistent with this view, we show that Polycomb Repressive Complex 2 (PRC2) silencing is genetically required by FCA to repress Overall, our work provides insights into RNA-mediated chromatin silencing.

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Proceedings of the National Academy of Sciences of the United States of America, 117, 26, 30 06 2020

PMID: 32541063

Open Access

Publisher Correction: ChromID identifies the protein interactome at chromatin marks.
Villaseñor R, Pfaendler R, Ambrosi C, Butz S, Giuliani S, Bryan E, Sheahan TW, Gable AL, Schmolka N, Manzo M, Wirz J, Feller C, von Mering C, Aebersold R, Voigt P, Baubec T

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Nature biotechnology, 38, 6, 06 2020

PMID: 32518402

bioRxiv Manuscripts

Nucleosomal Asymmetry Shapes Histone Mark Binding and Promotes Poising at Bivalent Domains
Elana Bryan, Marie Warburton, Kimberly M. Webb, Katy A. McLaughlin, Christos Spanos, Christina Ambrosi, Viktoria Major, Tuncay Baubec, Juri Rappsilber, Philipp Voigt
bioRxiv 2021.02.08.430127; doi:

The TAZ2 domain of CBP/p300 directs acetylation towards H3K27 within chromatin
Thomas W. Sheahan, Viktoria Major, Kimberly M. Webb, Elana Bryan, Philipp Voigt
bioRxiv 2020.07.21.214338; doi: