Overview
Our lab investigates the evolution of genome organisation, epigenetic gene regulation and chromosome architecture. We aim to better understand how genes are ordered along chromosomes, how genomes are organised and how tight co-ordinate gene regulation is achieved during organismic and environmental interactions.
Find our lab website here: https://genorglab.wordpress.com
Qualifications
2008 Biology/Diplom TU Dresden
2012 Dr. rer. nat. Leibniz-HKI and FSU Jena
Career
2022 – 2023: Royal Society University Research Fellow, Senior Research Fellow and proleptic Senior Lecturer, University of Exeter & University of Bath, UK
2022 – 2023: Royal Society University Research Fellow, Senior Research Fellow and proleptic Senior Lecturer, University of Bath, UK
2017 – 2022: Royal Society University Research Fellow and proleptic Lecturer, University of Bath, UK
2012 – 2017: EMBO Long-Term Fellow and Postdoctoral Researcher, John Innes Centre, Norwich, UK
2008 – 2012: PhD research, Leibniz Institute for Natural Product Research and Infection Biology/HKI Jena, Germany
Research group links
Research
Research projects
We are investigating genome organisation and gene regulation in plant, fungal and parasite systems. Find our current projects below.
How do adjacent genes become co-expressed: Regulation of metabolic gene clusters (The Royal Society)
Here, we investigate the molecular mechanisms that govern the co-ordinate expression of neighbouring genes in eukaryotes. We use metabolic gene clusters, neighbouring non-homologous genes that encode the pathway steps in the synthesis of bioactive specialised metabolites, as our model system. Specialised metabolites have important roles in plant defence and signalling. We aim to uncover the structural chromatin landscape at metabolic gene clusters and define their functional importance for cluster regulation. This work will provide fundamental insight into the transcriptional control of neighbouring genes and will provide essential information for advanced and safe implementation of gene technology in eukaryotes.
Genome plasticity in 3D – chromosomal rearrangements in plant defence (The Royal Society)
In this project, we study if and how the three-dimensional shape of chromosomes orchestrates the response of eukaryotic organisms to their biotic environment. We use core genetic elements of the immune system of plants to study conformational plasticity of chromosomes during host – pathogen interactions. This study will expand our knowledge of how plant genomes function and contribute to an improved understanding of how plants respond to the ever-changing challenges in their environment.
Epigenetic control of strawberry secondary metabolism - a small fruit with a complex genome (BBSRC SWBio DTP together with Hilary Rogers, Cardiff University)
Here, we ask how genome complexity and higher-order gene regulatory mechanisms act on aroma and nutritional value of strawberries. We are particularly interested in changes to chromatin, gene transcription and the metabolome post-harvest and in cold-storage.
Analyzing transposable element integration patterns in the 3D genome of plants (The Royal Society; a joint project with Alex Bousios, University of Sussex, and Davide Michielleto, University of Edinburgh)
In this project, we study the proliferation of transposable elements in plant genomes. We are interested in how the constraints of three-dimensional nuclear and chromosome structure affect the integration of transposable elements into the host genome. This study will lead to new insights into the evolution of genomes and provide important information for plant breeding.
Understanding the Interaction Between Introgressed DNA and the Wider Wheat Genome (Bristol Centre for Agricultural Innovation and BBSRC SWBIO DTP, a joint project with Keith Edwards, University of Bristol)
Here, we study the interplay between introgressed DNA elements and the host genome. This project will result in a better understanding of modern breeding processes.
The role of 'parasitism islands' in infection by soil-transmitted helminths (GW4 BioMed2 MRC DTP, a joint project with Vicky Hunt, University of Bath)
In this project, we will investigate the role and organisation of parasitism islands in nematodes. Our study will help us to better understand the genetic toolbox used by parasites to successfully infect the host.
Publications
Key publications | Publications by category | Publications by year
Publications by category
Journal articles
Nguyen TH, Thiers L, Van Moerkercke A, Bai Y, Fernández-Calvo P, Minne M, Depuydt T, Colinas M, Verstaen K, Van Isterdael G, et al (2023). A redundant transcription factor network steers spatiotemporal Arabidopsis triterpene synthesis. Nature Plants, 9(6), 926-937.
Zhao H, Yang M, Bishop J, Teng Y, Cao Y, Beall BD, Li S, Liu T, Fang Q, Fang C, et al (2022). Identification and functional validation of super-enhancers in. <i>Arabidopsis thaliana</i>.
Proceedings of the National Academy of Sciences,
119(48).
Abstract:
Identification and functional validation of super-enhancers in. Arabidopsis thaliana
. Super-enhancers (SEs) are exceptionally large enhancers and are recognized to play prominent roles in cell identity in mammalian species. We surveyed the genomic regions containing large clusters of accessible chromatin regions (ACRs) marked by deoxyribonuclease (DNase) I hypersensitivity in
. Arabidopsis thaliana
. We identified a set of 749 putative SEs, which have a minimum length of 1.5 kilobases and represent the top 2.5% of the largest ACR clusters. We demonstrate that the genomic regions associating with these SEs were more sensitive to DNase I than other nonpromoter ACRs. The SEs were preferentially associated with topologically associating domains. Furthermore, the SEs and their predicted cognate genes were frequently associated with organ development and tissue identity in
. A. thaliana
. Therefore, the
. A. thaliana
. SEs and their cognate genes mirror the functional characteristics of those reported in mammalian species
.
. We developed CRISPR/Cas-mediated deletion lines of a 3,578-bp SE associated with the thalianol biosynthetic gene cluster (BGC). Small deletions (131–157 bp) within the SE resulted in distinct phenotypic changes and transcriptional repression of all five thalianol genes. In addition, T-DNA insertions in the SE region resulted in transcriptional alteration of all five thalianol genes. Thus, this SE appears to play a central role in coordinating the operon-like expression pattern of the thalianol BGC.
.
Abstract.
Hao X, Xie C, Ruan Q, Zhang X, Wu C, Han B, Qian J, Zhou W, Nuetzmann H-W, Kai G, et al (2021). The transcription factor OpWRKY2 positively regulates the biosynthesis of the anticancer drug camptothecin in Ophiorrhiza pumila.
HORTICULTURE RESEARCH,
8(1).
Author URL.
Yu N, Nützmann HW, Macdonald JT, Moore B, Field B, Berriri S, Trick M, Rosser SJ, Kumar SV, Freemont PS, et al (2016). Delineation of metabolic gene clusters in plant genomes by chromatin signatures.
Nucleic Acids Research,
44(5), 2255-2265.
Abstract:
Delineation of metabolic gene clusters in plant genomes by chromatin signatures
Plants are a tremendous source of diverse chemicals, including many natural product-derived drugs. It has recently become apparent that the genes for the biosynthesis of numerous different types of plant natural products are organized as metabolic gene clusters, thereby unveiling a highly unusual form of plant genome architecture and offering novel avenues for discovery and exploitation of plant specialized metabolism. Here we show that these clustered pathways are characterized by distinct chromatin signatures of histone 3 lysine trimethylation (H3K27me3) and histone 2 variant H2A.Z, associated with cluster repression and activation, respectively, and represent discrete windows of co-regulation in the genome. We further demonstrate that knowledge of these chromatin signatures along with chromatin mutants can be used to mine genomes for cluster discovery. The roles of H3K27me3 and H2A.Z in repression and activation of single genes in plants are well known. However, our discovery of highly localized operon-like co-regulated regions of chromatin modification is unprecedented in plants. Our findings raise intriguing parallels with groups of physically linked multi-gene complexes in animals and with clustered pathways for specialized metabolism in filamentous fungi.
Abstract.
Medema MH, Kottmann R, Yilmaz P, Cummings M, Biggins JB, Blin K, de Bruijn I, Chooi YH, Claesen J, Coates RC, et al (2015). Minimum Information about a Biosynthetic Gene cluster.
Nat Chem Biol,
11(9), 625-631.
Author URL.
Nuetzmann H-W, Osbourn A (2015). Regulation of metabolic gene clusters in Arabidopsis thaliana.
NEW PHYTOLOGIST,
205(2), 503-510.
Author URL.
Bohnert M, Nuetzmann H-W, Schroeckh V, Horn F, Dahse H-M, Brakhage AA, Hoffmeister D (2014). Cytotoxic and antifungal activities of melleolide antibiotics follow dissimilar structure-activity relationships.
PHYTOCHEMISTRY,
105, 101-108.
Author URL.
Nuetzmann H-W, Osbourn A (2014). Gene clustering in plant specialized metabolism.
CURRENT OPINION IN BIOTECHNOLOGY,
26, 91-99.
Author URL.
Nuetzmann H-W, Fischer J, Scherlach K, Hertweck C, Brakhage AA (2013). Distinct Amino Acids of Histone H3 Control Secondary Metabolism in Aspergillus nidulans.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY,
79(19), 6102-6109.
Author URL.
Nuetzmann H-W, Reyes-Dominguez Y, Scherlach K, Schroeckh V, Horn F, Gacek A, Schuemann J, Hertweck C, Strauss J, Brakhage AA, et al (2011). Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
108(34), 14282-14287.
Author URL.
Scherlach K, Nuetzmann H-W, Schroeckh V, Dahse H-M, Brakhage AA, Hertweck C (2011). Cytotoxic Pheofungins from an Engineered Fungus Impaired in Posttranslational Protein Modification.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,
50(42), 9843-9847.
Author URL.
Schroeckh V, Scherlach K, Nuetzmann H-W, Shelest E, Schmidt-Heck W, Schuemann J, Martin K, Hertweck C, Brakhage AA (2009). Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
106(34), 14558-14563.
Author URL.
Chapters
Nuetzmann H-W, Schroeckh V, Brakhage AA (2012). Regulatory Cross Talk and Microbial Induction of Fungal Secondary Metabolite Gene Clusters. In (Ed)
NATURAL PRODUCT BIOSYNTHESIS BY MICROORGANISMS AND PLANTS, PT C, 325-341.
Author URL.
Publications by year
2023
Nguyen TH, Thiers L, Van Moerkercke A, Bai Y, Fernández-Calvo P, Minne M, Depuydt T, Colinas M, Verstaen K, Van Isterdael G, et al (2023). A redundant transcription factor network steers spatiotemporal Arabidopsis triterpene synthesis. Nature Plants, 9(6), 926-937.
2022
Zhao H, Yang M, Bishop J, Teng Y, Cao Y, Beall BD, Li S, Liu T, Fang Q, Fang C, et al (2022). Identification and functional validation of super-enhancers in. <i>Arabidopsis thaliana</i>.
Proceedings of the National Academy of Sciences,
119(48).
Abstract:
Identification and functional validation of super-enhancers in. Arabidopsis thaliana
. Super-enhancers (SEs) are exceptionally large enhancers and are recognized to play prominent roles in cell identity in mammalian species. We surveyed the genomic regions containing large clusters of accessible chromatin regions (ACRs) marked by deoxyribonuclease (DNase) I hypersensitivity in
. Arabidopsis thaliana
. We identified a set of 749 putative SEs, which have a minimum length of 1.5 kilobases and represent the top 2.5% of the largest ACR clusters. We demonstrate that the genomic regions associating with these SEs were more sensitive to DNase I than other nonpromoter ACRs. The SEs were preferentially associated with topologically associating domains. Furthermore, the SEs and their predicted cognate genes were frequently associated with organ development and tissue identity in
. A. thaliana
. Therefore, the
. A. thaliana
. SEs and their cognate genes mirror the functional characteristics of those reported in mammalian species
.
. We developed CRISPR/Cas-mediated deletion lines of a 3,578-bp SE associated with the thalianol biosynthetic gene cluster (BGC). Small deletions (131–157 bp) within the SE resulted in distinct phenotypic changes and transcriptional repression of all five thalianol genes. In addition, T-DNA insertions in the SE region resulted in transcriptional alteration of all five thalianol genes. Thus, this SE appears to play a central role in coordinating the operon-like expression pattern of the thalianol BGC.
.
Abstract.
2021
Hao X, Xie C, Ruan Q, Zhang X, Wu C, Han B, Qian J, Zhou W, Nuetzmann H-W, Kai G, et al (2021). The transcription factor OpWRKY2 positively regulates the biosynthesis of the anticancer drug camptothecin in Ophiorrhiza pumila.
HORTICULTURE RESEARCH,
8(1).
Author URL.
2019
Bousios A, Nuetzmann H-W, Buck D, Michieletto D (2019). Integrating Transposable Elements in the 3D Genome.
Abstract:
Integrating Transposable Elements in the 3D Genome
Chromosome organisation is increasingly recognised as an essential component
of genome regulation, cell fate and cell health. Within the realm of
transposable elements (TEs) however, the spatial information of how genomes are
folded is still only rarely integrated in experimental studies or accounted for
in modelling. Here, we propose a new predictive modelling framework for the
study of the integration patterns of TEs based on extensions of widely employed
polymer models for genome organisation. Whilst polymer physics is recognised as
an important tool to understand the mechanisms of genome folding, we now show
that it can also offer orthogonal and generic insights into the integration and
distribution profiles (or "topography") of TEs across organisms. Here, we
present polymer physics arguments and molecular dynamics simulations on TEs
inserting into heterogeneously flexible polymers and show with a simple model
that polymer folding and local flexibility affects TE integration patterns. The
preliminary discussion presented herein lay the foundations for a large-scale
analysis of TE integration dynamics and topography as a function of the
three-dimensional host genome.
Abstract.
Author URL.
2016
Yu N, Nützmann HW, Macdonald JT, Moore B, Field B, Berriri S, Trick M, Rosser SJ, Kumar SV, Freemont PS, et al (2016). Delineation of metabolic gene clusters in plant genomes by chromatin signatures.
Nucleic Acids Research,
44(5), 2255-2265.
Abstract:
Delineation of metabolic gene clusters in plant genomes by chromatin signatures
Plants are a tremendous source of diverse chemicals, including many natural product-derived drugs. It has recently become apparent that the genes for the biosynthesis of numerous different types of plant natural products are organized as metabolic gene clusters, thereby unveiling a highly unusual form of plant genome architecture and offering novel avenues for discovery and exploitation of plant specialized metabolism. Here we show that these clustered pathways are characterized by distinct chromatin signatures of histone 3 lysine trimethylation (H3K27me3) and histone 2 variant H2A.Z, associated with cluster repression and activation, respectively, and represent discrete windows of co-regulation in the genome. We further demonstrate that knowledge of these chromatin signatures along with chromatin mutants can be used to mine genomes for cluster discovery. The roles of H3K27me3 and H2A.Z in repression and activation of single genes in plants are well known. However, our discovery of highly localized operon-like co-regulated regions of chromatin modification is unprecedented in plants. Our findings raise intriguing parallels with groups of physically linked multi-gene complexes in animals and with clustered pathways for specialized metabolism in filamentous fungi.
Abstract.
2015
Medema MH, Kottmann R, Yilmaz P, Cummings M, Biggins JB, Blin K, de Bruijn I, Chooi YH, Claesen J, Coates RC, et al (2015). Minimum Information about a Biosynthetic Gene cluster.
Nat Chem Biol,
11(9), 625-631.
Author URL.
Nuetzmann H-W, Osbourn A (2015). Regulation of metabolic gene clusters in Arabidopsis thaliana.
NEW PHYTOLOGIST,
205(2), 503-510.
Author URL.
2014
Bohnert M, Nuetzmann H-W, Schroeckh V, Horn F, Dahse H-M, Brakhage AA, Hoffmeister D (2014). Cytotoxic and antifungal activities of melleolide antibiotics follow dissimilar structure-activity relationships.
PHYTOCHEMISTRY,
105, 101-108.
Author URL.
Nuetzmann H-W, Osbourn A (2014). Gene clustering in plant specialized metabolism.
CURRENT OPINION IN BIOTECHNOLOGY,
26, 91-99.
Author URL.
2013
Nuetzmann H-W, Fischer J, Scherlach K, Hertweck C, Brakhage AA (2013). Distinct Amino Acids of Histone H3 Control Secondary Metabolism in Aspergillus nidulans.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY,
79(19), 6102-6109.
Author URL.
2012
Nuetzmann H-W, Schroeckh V, Brakhage AA (2012). Regulatory Cross Talk and Microbial Induction of Fungal Secondary Metabolite Gene Clusters. In (Ed)
NATURAL PRODUCT BIOSYNTHESIS BY MICROORGANISMS AND PLANTS, PT C, 325-341.
Author URL.
2011
Nuetzmann H-W, Reyes-Dominguez Y, Scherlach K, Schroeckh V, Horn F, Gacek A, Schuemann J, Hertweck C, Strauss J, Brakhage AA, et al (2011). Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
108(34), 14282-14287.
Author URL.
Scherlach K, Nuetzmann H-W, Schroeckh V, Dahse H-M, Brakhage AA, Hertweck C (2011). Cytotoxic Pheofungins from an Engineered Fungus Impaired in Posttranslational Protein Modification.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,
50(42), 9843-9847.
Author URL.
2009
Schroeckh V, Scherlach K, Nuetzmann H-W, Shelest E, Schmidt-Heck W, Schuemann J, Martin K, Hertweck C, Brakhage AA (2009). Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
106(34), 14558-14563.
Author URL.
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