HDAC HEMATOPOIESIS

Role of Class IIa Histone deacetylases in hematopoietic cell differentiation

Coordinatore	FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE    more  Organization address address: AVENIDA GRAN VIA HOSPITALET 199-203 city: L'HOSPITALET DE LLOBREGAT postcode: 8908 contact info Titolo: Ms. Nome: Carole Cognome: Amroune Email: send email Telefono: 34932607245 Fax: 34932607219
Nazionalità Coordinatore	Spain [ES]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2007-4-3-IRG
Funding Scheme	MC-IRG
Anno di inizio	2007
Periodo (anno-mese-giorno)	2007-09-01   -   2011-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE  Organization address address: AVENIDA GRAN VIA HOSPITALET 199-203 city: L'HOSPITALET DE LLOBREGAT postcode: 8908 contact info Titolo: Ms. Nome: Carole Cognome: Amroune Email: send email Telefono: 34932607245 Fax: 34932607219	ES (L'HOSPITALET DE LLOBREGAT)	coordinator	0.00
2	FUNDACIO CENTRE DE REGULACIO GENOMICA  Organization address address: CARRER DOCTOR AIGUADER 88 city: BARCELONA postcode: 8003 contact info Titolo: Dr. Nome: Thomas Cognome: Graf Email: send email Telefono: -3160186 Fax: -3970042	ES (BARCELONA)	participant	0.00

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 Obiettivo del progetto (Objective)

'Chromatin, the higher order structure of DNA and protein, forms a barrier for gene transcription. Modification of histones, a major component of the chromatin, is a critical mechanism by which the barrier is regulated. An important modification, which is thought to activate transcription, is the acetylation of histones. Regulation of histones acetylation is performed by the antagonistic activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Mammalian HDACs are divided into three distinct classes based on their homology to yeast proteins. Class I HDACs (HDAC1, 2, 3 and 8), Class II HDACs, which are subdivided into two families, Class IIa (HDAC4, 5, 7 and 9) and Class IIb (HDAC6 and 10) and Class III HDACs, also named sirtuins, which comprises Sirt1, 2, 3, 4, 5, 6 and 7. In contrast to other HDACs, Class IIa HDACs are expressed in a tissue specific manner and have been shown to play an important role in cell differentiation. The hematopoietic system is a complex and interesting model of cell commitment and differentiation. Hematopoietic lineages are specified by lineage-restricted transcription factors that result in a distinct gene expression pattern. However, little is known about the role of chromatin modifying enzymes in the hematopoietic system. It has been shown that HDAC5 and HDAC9 are expressed in hematopoietic cells. However, their role in commitment of hematopoietic cells has never been investigated. Here, I propose to study the role of HDAC5 and HDAC9 in lineage commitment of hematopoietic cells. By using a genomic approach, as well as, knock out and trangenic mouse models, I will elucidate the lineage compartment where they are expressed, the specific target genes repressed by both proteins and their role in hematopoietic cell differentiation. The elucidation of the molecular mechanisms involved in the lineage commitment of hematopoietic stem cells will suppose an important advance in regenerative medicine.'

Introduzione (Teaser)

Blood cells originate from a small pool of hematopoietic stem cells (HSCs) through a complex process of differentiation steps that are tightly regulated at the transcriptional level. Dissecting the mechanisms underlying this control will aid the understanding of how these particular cellular states are generated.