Team
Epigenetic Regulations
Dpt: Signaling through Chromatin
Our research activities
Considering the extreme nature of epigenetic regulations operating in maturing male haploid cells, our team has made several major discoveries, shedding new light on the obscure process of sperm epigenome establishment, with conceptual impacts in the field of epigenetics in general. These discoveries concern the biology of bromodomain factors, the biology of histone variants and histone acetyltransferases, and new histone languages based on non-acetylated histone acylations. This has led us more recently to develop a new research axis on the link between metabolism and epigenome in various physio-pathological contexts, including cancer. Our team is also developing EpiMed, an "in silico" epigenetics axis, involving a dedicated group of experts in concept-driven "omics" data analysis. New information on epigenetic regulations is extracted from various “omics” data leading to the discovery of cancer biomarkers, the identification of new therapeutic approaches, and oncogenic mechanisms. In addition, EpiMed also positions us in new research areas such as population epigenetics. The strong and visible activity of our team places us at the center of many international collaborative projects, partly managed by an International Associated Laboratory (LIA) with the Shanghai Institute of Haematology (JiaoTong University). Within this framework, several projects involving computational epigenetics and the metabolism-epigenetics dialogue are under development in various cancer types.
Saadi KHOCHBIN
Team leader, Platform manager
04 76 54 95 83
Our research axes
We previously discovered the occurrence of unknown structural states that appear during histone-to-protamine (PRM) replacement (2007; 2013; 2017). The objective of this research line is to understand the structural and functional basis of these transient genome organizational states.
We and others have established that a general and physiological hyperacetylation of histone H4 occurs at the time of histone replacement by protamines (PRMs) (2000). The cause of this hyperacetylation and its consequences on the reorganization of the post-meiotic male genome have long remained a mystery. The objective of this particular line of research is to discover the molecular mechanisms at the origin of this massive hyperacetylation of histone H4 (2010; 2018; 2022).
We have previously identified a testis-specific bromodomain-containing factor, BRDT, as an important player in acetylation-dependent chromatin reorganization (2003). The aim of this line of research is to use extensive structural (2009; 2016) and functional (2012; 2016) analyses to decipher the role of BRDT, as well as other testis-specific bromodomain-containing factors such as ATAD2 (2015; 2021), in hyperacetylation-dependent histone eviction.
Our early collaborative work on histone lysine acylations with Prof. Y ZHAO (U. Chicago, USA) showed that histone acylations could be important epigenetic players (2011; 2013; 2014; 2016; 2021). With D. PANNE (U. Leicester, UK), the structural basis for the action of p300 in mediating histone acylations has been established (2017). This work highlights two important paradigm-changing concepts: 1) the metabolically driven competition between histone acetylation and acylation; and 2) its impact on bromodomain factor biology in general (2016; 2021)…
This line of research, which has been developing rapidly in recent years, builds on our recent findings on the role of the bromodomain factor ATAD2 in chromatin dynamics (2010; 2015; 2021), the dynamics of bromodomain factor binding through the acetylation/acylation ratio (2021), and finally, the role of the concurrent metabolic pathways in epigenetic reprogramming.
This research is carried out by the EpiMed members of our team who are experts in concept-driven "omics" data analysis in order to develop innovative approaches, in particular in the discovery of cancer biomarkers (so far, 9 independent cancer types have been considered) and in population epigenetics (environmental epidemiology and physiology). This program also involves all the university hospital members of the team (5 medical/clinical professors and associated staff).
Our major publications
See all publicationsOur activities in pictures
Our collaborations
- Pr. Daniel Panne, Leicester Institute of Structural and Chemical Biology (University of Leicester). Structural basis of p300 activation and p300-mediated histone acylation (6 published research articles).
- Pr. Yingming Zhao, University of Chicago. Functional studies of histone acylations (9 published research articles and 1 review).
- Dr. Carlo Petosa, Institut de Biologie Structurale, bromodomain/histone structure/function (6 published research articles and 1 review).
- Pr. Mi/Wang, Loboratoire International Associé (Grenoble-Shanghai) (10 published articles, and 3 reviews).
- Pr. Minoru Yoshida, Riken/Tokyo University. Acetylation biology (11 published articles, and 2 reviews)
- In addition to these examples, we are coordinating important international networks of world-class leaders. Most of our high impact publications in fact involve between 5 to 10 international laboratories from Asia (China and Japan), Europe, and USA.
Our technologies
- All the cutting-edge molecular/chromatin biology laboratory technics
- Development of various mouse models (post-meiotic spermatogenesis, lung and liver cancers, etc…)
- All the bioinformatics/biostatistics/artificial intelligence approaches