Publications by Beat Fierz | EPFL Graph Search

Structural basis of SIRT7 nucleosome engagement and substrate specificity

Henning Paul-Julius Stahlberg, Beat Fierz, Dongchun Ni, Babatunde Edukpe Ekundayo, Carlos Moreno Yruela

Chromatin-modifying enzymes target distinct residues within histones to finetune gene expression profiles. SIRT7 is an NAD+-dependent deacylase often deregulated in cancer, which deacetylates either H3 lysine 36 (H3K36) or H3K18 with high specificity withi ...

NATURE PORTFOLIO2025

MagIC beads for scarce macromolecules

Beat Fierz, Carlos Moreno Yruela

Specialized magnetic beads that bind target proteins to a cryogenic electron microscopy grid make it possible to study the structure of protein complexes from dilute samples. ...

eLIFE SCIENCES PUBL LTD2025

Peptide‐Carbazolyl Cyanobenzene Conjugates: Enabling Biomolecule Functionalization via Photoredox and Energy Transfer Catalysis

Anne-Sophie Chauvin, Jérôme Waser, Beat Fierz, Xingyu Liu, Wei Cai

Since their discovery in 2012, carbazolyl (iso)phthalonitrile derivatives (Cz(I)PN) have found significant applications as photocatalysts in organic chemistry. Herein, we introduce two efficient methods for incorporating carbazolyl cyanobenzenes into vario ...

Wiley2025

Single-molecule analysis reveals the mechanism of chromatin ubiquitylation by variant PRC1 complexes

Beat Fierz, Alexandra Teslenko

Chromatin regulation relies on “writer” enzymes that add posttranslational modifications to histone proteins. Variant polycomb repressive complex 1 (PRC1) exists as several subtypes, which are “writers” of ubiquitylation on histone H2A K118 and K119, cruci ...

American Association for the Advancement of Science (AAAS)2025

The HP1 box of KAP1 organizes HP1α for silencing of endogenous retroviral elements in embryonic stem cells

Rudolf Hovius, Matteo Dal Peraro, Beat Fierz, Maria Josefina Marcaida Lopez

Repression of endogenous retroviral elements (ERVs) is facilitated by KAP1 (KRAB-associated protein 1)-containing complexes, however the underlying mechanism remains unclear. Here, we show that binding of KAP1 to the major component of the heterochromatin ...

Springer Science and Business Media LLC2025

Semisynthesis of Isomerized Histone H4 Reveals Robustness and Vulnerability of Chromatin toward Molecular Aging

Beat Fierz

Proteins are subject to aging in the form of spontaneous, nonenzymatic post-translational modifications (PTMs). One such PTM is the formation of the β-linked isomer l-isoaspartic acid (isoAsp) from aspartic acid (Asp) or asparagine residues, which tends to ...

2025

Decoding Chromatin Ubiquitylation: A Chemical Biology Perspective

Beat Fierz, Pauline Franz

Since Strahl and Allis proposed the "language of covalent histone modifications", a host of experimental studies have shed light on the different facets of chromatin regulation by epigenetic mechanisms. Initially proposed as a concept for controlling gene ...

Academic Press Ltd- Elsevier Science Ltd2024

Revealing chromatin-specific functions of histone deacylases

Beat Fierz, Carlos Moreno Yruela

Histone deacylases are erasers of Nε-acyl-lysine post-translational modifications and have been targeted for decades for the treatment of cancer, neurodegeneration and other disorders. Due to their relatively promiscuous activity on peptide substrates in v ...

2024

A Site-Specific Click Chemistry Approach to Di-Ubiquitylate H1 Variants Reveals Position-Dependent Stimulation of the DNA Repair Protein RNF168

Beat Fierz, Pauline Franz

Ubiquitylation of histone H2A at lysines 13 and 15 by the E3 ligase RNF168 plays a key role in orchestrating DNA double-strand break (DSB) repair, which is often deregulated in cancer. RNF168 activity is triggered by DSB signaling cascades, reportedly thro ...

Wiley-VCH Verlag GmbH2024

Synthesis of Fluorescent Cyclic Peptides via Gold(I)-Catalyzed Macrocyclization

Aleksandra Radenovic, Jérôme Waser, Beat Fierz, Xingyu Liu, Nathan Cyprien Arsène Ronceray, Wei Cai

Rapid and efficient cyclization methods that form structurally novel peptidic macrocycles are of high importance for medicinal chemistry. Herein, we report the first gold(I)-catalyzed macrocyclization of peptide-EBXs (ethynylbenziodoxolones) via C2-Trp C–H ...

2023

CENP-A and CENP-B collaborate to create an open centromeric chromatin state

Beat Fierz, Harsh Nagpal, Wei Cai

Centromeres are epigenetically defined via the presence of the histone H3 variant CENP-A. Contacting CENP-A nucleosomes, the constitutive centromere associated network (CCAN) and the kinetochore assemble, connecting the centromere to spindle microtubules d ...

Nature Portfolio2023

Cooperation between bHLH transcription factors and histones for DNA access

Beat Fierz, Kristina Makasheva

The basic helix-loop-helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members(1). Here we investigate how chromatinized E-boxes are engaged by two structurally diverse bHLH proteins: the proto-on ...

NATURE PORTFOLIO2023

De novo design of protein interactions with learned surface fingerprints

Henning Paul-Julius Stahlberg, Didier Trono, Priscilla Turelli, Charlène Mireille Raymonde Raclot, Sandrine Madeleine Suzanne Georgeon, Beat Fierz, Aaron Simone Petruzzella, Anthony Marchand, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Zander Harteveld, Pablo Gainza Cirauqui, Freyr Sverrisson, Andreas Scheck, Sarah Wehrle, Stéphane Rosset, Alexandra Krina Van Hall-Beauvais, Alexandra Teslenko, Jane Marsden, Michael Bronstein, Casper Alexander Goverde, Stephen Michael Buckley, Dongchun Ni, Martin Pacesa

Physical interactions between proteins are essential for most biological processes governing life. However, the molecular determinants of such interactions have been challenging to understand, even as genomic, proteomic and structural data increase. This k ...

2023

Short talk Single-molecule enzymology of chromatin ubiquitination

Beat Fierz, Alexandra Teslenko

SPRINGER2023

Tubulin engineering by semi-synthesis reveals that polyglutamylation directs detyrosination

Luc Reymond, Pierre Gönczy, Nora Guidotti, Beat Fierz, Ninad Dilip Agashe, Georgios Hatzopoulos, Timothy Matthias Reichart, Eduard Hubert Theodoor Marius Ebberink, Fabian Zacharias Schneider, Cédric Pourroy, Po-Han Chang

Microtubules, a critical component of the cytoskeleton, carry post-translational modifications (PTMs) that are important for the regulation of key cellular processes. Long-lived microtubules, in neurons particularly, exhibit both detyrosination of a-tubuli ...

NATURE PORTFOLIO2023

Target search dynamics of Sox transcription factors

Beat Fierz, David Michael Suter, Sim Sakong

CELL PRESS2023

PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of chromatin compaction

Beat Fierz, Iuliia Boichenko

The Polycomb repressive complexes PRC1, PRC2, and PR-DUB repress target genes by modifying their chromatin. In Drosophila, PRC1 compacts chromatin and monoubiquitinates histone H2A at lysine 118 (H2Aub1), whereas PR-DUB is a major H2Aub1 deubiquitinase, bu ...

2022

Multiplexed single-molecule experiments reveal Cas9 nucleosome invasion dynamics

Louise Catherine Bryan, Beat Fierz, Kristina Makasheva

CELL PRESS2022

Release of linker histone from the nucleosome driven by polyelectrolyte competition with a disordered protein

Beat Fierz, Sinan Kilic

Highly charged intrinsically disordered proteins are essential regulators of chromatin structure and transcriptional activity. Here we identify a surprising mechanism of molecular competition that relies on the pronounced dynamical disorder present in thes ...

NATURE PORTFOLIO2022

Multivalent Peptide Ligands To Probe the Chromocenter Microenvironment in Living Cells

Nora Guidotti, Maxime Nicolas Mivelaz, Beat Fierz, Pablo Rivera Fuentes, Adam Miklos Eördögh

Chromatin is spatially organized into functional states that are defined by both the presence of specific histone post-translational modifications (PTMs) and a defined set of chromatin-associated “reader” proteins. Different models for the underlying mecha ...

2022