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Linker histones at the nexus of plant cell reprogramming

English title Linker histones at the nexus of plant cell reprogramming
Applicant Baroux Célia
Number 185186
Funding scheme Project funding (Div. I-III)
Research institution Institut für Pflanzen- und Mikrobiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Embryology, Developmental Biology
Start/End 01.09.2019 - 31.08.2023
Approved amount 559'826.00
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All Disciplines (4)

Discipline
Embryology, Developmental Biology
Genetics
Cellular Biology, Cytology
Molecular Biology

Keywords (7)

Linker Histone; citrullination; chromatin; development, reproduction; Arabidopsis; cell fate; microscopy imaging, image processing

Lay Summary (French)

Lead
L'information génétique des eucaryotes est organisée dans le noyau cellulaire sous la forme d'un assemblage complexe entre l'ADN et des protéines spécalisées, les histones, formant la chromatine. Historiquement décrit comme une substance colorée, la chromatine se révèle être une structure moléculaire très élaborée dont la composition et la structure influence l'expression des gènes. Un des objectifs de la recherche dans le domaine de l'épigénétique est d'élucider ce lien composition-structure-fonction. Notre project a pour but de contribuer à cette question en étudiant notemment le rôle des variants d'histones dits H1 ou "linker histones", lors de la reprogrammation cellulaire, en particulier chez les plantes.
Lay summary
La chromatine est l'assemblage de l'ADN enroulé de manière régulière et régulée autour d'un complexe multiprotéique d'histones. La fibre chromatinienne peut adopter différents degrés d'organisation supra-moléculaires et de compaction influencant l'accessibilité des gènes aux facteurs de transcription. La modification des histones elles-mêmes par couplage d'un groupe biochimique, a également une influence sur la structure de la chromatine et son affinité locale avec les régulateurs transcriptionnels. Ces modifications dites épigénétiques influencent donc l'expression des gènes. Un autre acteur de l'organisation chromatinienne est l'histone H1. Cet histone est présent sous forme de différents variants, eux mêmes pouvant être modifiés de manière post-traductionnelle. Longtemps considérés comme de simples architectes structurants de la chromatine, les variants H1 semblent jouer des rôles plus subtils en influencant d'autres marques épigénétiques ainsi que l'arrangement spatial des domaines chromatiniens dans le noyau.
Nous utilisons des approches génétiques, moléculaires et cytologiques sur la plante modèle Arabidopsis pour décrire en particulier le rôle de deux variants H1 et leur modification(s), sur deux modèles de dynamique cellulaire: (i) lors de la mise en place de la lignée reproductrice (formant les gamètes) (ii) lors des réponses transcriptionnelles aux changements diurnaux. Notre recherche s'inscrit dans l'objectif de comprendre le role des variants H1 au cours de dynamiques cellulaires lors du développement et lors de réponses à un stimulus environnemental chez les plantes. 
Direct link to Lay Summary Last update: 07.05.2019

Lay Summary (English)

Lead
The genetic material of eukaryotes is packed together with proteins into an elaborated structure, called the chromatin. Initially discovered as a colorable substance in cytological preparations, the chromatin is now known as a modular molecular complex which greatly influences gene expression. The challenge of the epigenetic field of research is to decrypt the different forms at the molecular, nano and microscale and detailed composition of chromatin states in relation to their function. Our research contributes to this challenge by exploring the role of specific chromatin architects, the linker histones.
Lay summary

Chromatin provides a tunable, molecular platform for controlling gene expression in eucaryotes. Biochemical modifications of the DNA and nucleosome histones are a major component of the epigenetic code. Besides, higher-order-level chromatin organization and in fine gene expression is also influenced by chromatin architects such as the linker histones (H1). Long thought to be only structural, the repertoire of H1 roles has been considerably extended in recent years, with for instance a central role in mammalian cells pluripotency. Plant cells like animal cells also comprise a complement of H1 variants but their function is far from being elucidated. Our research aim at elucidating the role of H1 in the model plant Arabidopsis particularly in relation to cellular reprogramming under developmental and environmental cues. For this, we are using a combination of genetic, molecular and cytological approaches and are focusing on two study cases involving H1 function: (i) the somatic-to-reproductive transition; (ii) transcriptional responses under diurnal light rythms. Collectively, we hope to shed light on the contribution of high-order chromatin organisation, mediated by H1, to general reprogramming processes underlying cellular responses and plasticity in plants. 

Direct link to Lay Summary Last update: 07.05.2019

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
182949 Role of linker histones in plant tissue regeneration 01.01.2019 COST (European Cooperation in Science and Technology)

Abstract

Background. Chromatin provides a tunable, molecular platform for controlling gene expression in eucaryotes. Biochemical modifications of the DNA and nucleosome histones are a major component of the epigenetic code. Besides, higher-order-level chromatin organization and in fine gene expression is also influenced by chromatin architects such as the linker histones (H1). Long thought to be only structural, the repertoire of H1 roles has been considerably extended in recent years, with for instance a central role in mammalian cells pluripotency. Plant cells like animal cells also comprise a complement of H1 variants but their function is far from being elucidated. Our research aim at elucidating the role of H1 in Arabidopsis particularly in relation to cellular reprogramming under developmental and environmental cues. At the developmental level, we previously showed that H1 variants are evicted from spore mother cells (SMCs) just prior to meiosis in Arabidopsis. H1 eviction precedes a drastic chromatin reorganization correlated with the post-meiotic developmental competence. We recently identified a key arginine residue controlling H1 stability and influencing in turn SMC fate. Hypothesis 1: Based on preliminary evidence, we formulate the hypothesis that arginine citrullination, a modification which has never been described In plants, is a key regulator of H1 and plays a role during reprogramming at the somatic-to-reproductive transition. At the level of environmental responses, we recently measured lower performance of H1-depleted plants under alternating light regimes compared to continuous light. Hypothesis 2. H1 acts as a facilitator of transcriptional reprogramming in changing environment, such as light regimes.Objectives. We will characterize the functional role of H1 (and its post-translational regulation) during cellular reprogramming, focusing on one developmental transition (somatic-to-reproductive) and one environmental response (light regime)Specific Aims. We will characterize H1 citrullination and its putative modifying enzyme at the molecular and biochemical level using enzymatic assays, customized nanobodies and available mutant variants in Arabidopsis (project A). In a pilot project we will establish a proof-of-concept study addressing the role of H1 is securing robust transcriptional output in response to diurnal changes (Project B). The work relies on a large amount of material and methods established in the group, a long-lasting expertise in chromatin analyses and collaborations securing deliverables on novel biochemical and molecular approaches. Impact and Relevance. This work will shed light on the functional link between H1 dynamics and cell fate competence, contribute methodological and biological advances to the field while contributing our understanding of plant cell reprogramming with broad implication to cellular plasticity in plant development and plant responses to the environment.
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