Obiettivo Cell type specific organization of DNA into chromatin is an important determinant of gene expression and cell identity. During cell division, epigenetic information in chromatin must be transmitted to daughter cells in order to maintain cell identity or commit to a developmental program. However, it remains unknown how epigenetic states are inherited during cell division. Elucidating molecular mechanisms underlying epigenetic cell memory thus represents a major challenge in biology critical to understand development and disease.Chromatin undergoes genome-wide disruption during DNA replication and histone marks are diluted 2-fold due to new histone deposition. Yet, how this impacts on establishment and maintenance of gene expression programs is not known. I hypothesize that chromatin replication represents a critical window for epigenetic cell memory and cell fate decisions, and predict that three histone-based processes play critical roles in guarding cell identity: 1) new histone deposition to regulate nucleosome occupancy and transcription factor (TF) binding, 2) accurate transmission of old modified histones by dedicated recycling machinery, and 3) recruitment of regulatory proteins to new and old histones to direct epigenome maintenance. To dissect these events mechanistically and test causal roles in cell fate decisions, I propose a research program integrating explorative proteomics and histone chaperone structure-function analysis with stem cell biology and new cutting-edge genomic tools developed by my research group. The proposed research will 1) identify novel mechanisms of histone chaperoning and deposition specific to new and old histones, 2) reveal how nucleosome assembly govern TF binding during DNA replication, and 3) address the significance of old histone recycling and new histone deposition for pluripotency and commitment. This will provide a major advance in understanding the molecular mechanisms that govern epigenetic cell memory. Campo scientifico ingegneria e tecnologiaingegneria ambientalegestione dei rifiutiprocessi di trattamento dei rifiutiriciclaggioscienze naturaliscienze biologichegeneticaDNAscienze naturaliscienze biologichebiologia cellularescienze mediche e della salutebiotecnologia medicatecnologie cellularicellule staminaliscienze naturaliscienze biologichegeneticaepigenetica Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2016-COG - ERC Consolidator Grant Invito a presentare proposte ERC-2016-COG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Coordinatore KOBENHAVNS UNIVERSITET Contribution nette de l'UE € 1 999 750,00 Indirizzo Norregade 10 1165 Kobenhavn Danimarca Mostra sulla mappa Regione Danmark Hovedstaden Byen København Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Altri finanziamenti € 0,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto KOBENHAVNS UNIVERSITET Danimarca Contribution nette de l'UE € 1 999 750,00 Indirizzo Norregade 10 1165 Kobenhavn Mostra sulla mappa Regione Danmark Hovedstaden Byen København Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Altri finanziamenti € 0,00
