EXPRES

Chromatin and transcription in ES cells: from single cells to genome wide views

 Coordinatore THE HEBREW UNIVERSITY OF JERUSALEM. 

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 Nazionalità Coordinatore Israel [IL]
 Totale costo 1˙500˙000 €
 EC contributo 1˙500˙000 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2011-StG_20101109
 Funding Scheme ERC-SG
 Anno di inizio 2011
 Periodo (anno-mese-giorno) 2011-12-01   -   2016-11-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    THE HEBREW UNIVERSITY OF JERUSALEM.

 Organization address address: GIVAT RAM CAMPUS
city: JERUSALEM
postcode: 91904

contact info
Titolo: Dr.
Nome: Eran
Cognome: Meshorer
Email: send email
Telefono: +972 2 6585161
Fax: +972 2 6586073

IL (JERUSALEM) hostInstitution 1˙500˙000.00
2    THE HEBREW UNIVERSITY OF JERUSALEM.

 Organization address address: GIVAT RAM CAMPUS
city: JERUSALEM
postcode: 91904

contact info
Titolo: Mr.
Nome: Hani
Cognome: Ben-Yehuda
Email: send email
Telefono: +972 2 6586676
Fax: +972 2 6513205

IL (JERUSALEM) hostInstitution 1˙500˙000.00

Mappa


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function    proteins    escs    plasticity    nuclease    selected    esc    regulation    chip    polyadenylated    fundamental    search    mechanisms    chromatin   

 Obiettivo del progetto (Objective)

'How embryonic stem cells (ESCs) maintain their dual capacity to self-renew and to differentiate into all cell types is one of the fundamental questions in biology. Although this question remains largely open, there is growing evidence suggesting that chromatin plasticity is a fundamental hallmark of ESCs, providing their necessary flexibility. Previously we found that ESCs possess a relatively open chromatin conformation, giving rise to permissive transcriptional program. Here I propose to investigate the mechanisms that support chromatin plasticity and pluripotency in ESCs. Using a simple biochemical assay which I developed (DCAP: Differential Chromatin Associated Proteins), based on micrococcal nuclease (MNase) digestion combined with multi-dimensional protein identification technology (MudPIT), I seek to identify ESC-specific chromatin proteins. Selected proteins will be knocked-down (or out) and their ESC function will be evaluated. In addition, I will conduct a hypothesis-driven research using mutant ESCs and epigenetic-related drugs to search for potential mechanisms, (i.e. histone modifications, DNA methylation), that may support chromatin plasticity in ESCs. Based on our intriguing preliminary data, I will also focus on the link between the nuclear lamina and ESC plasticity. Thirdly, we will analyze non-polyadenylated transcription using genome-wide tiling arrays and RNA-seq. We will design custom microarrays containing the identified sequences, which will allow us to reveal, using ChIP-chip experiments, the mechanistic regulation of the non-polyadenylated transcripts. Finally, we will knockout, using zinc-finger nuclease technology, selected highly conserved candidates in search of their function. Understanding chromatin regulation, plasticity and function will enable one to intelligently manipulate ESCs to transition between the pluripotent, multipotent and unipotent states and to expedite their use in the clinic.'

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