MSL1-MSL3-MOF

How protein complexes recognize and modify chromatin: Structural studies on MSL1-MSL3-MOF Dosage Compensation Complex bound to nucleosomes

Coordinatore	MEDICAL RESEARCH COUNCIL    more  Organization address address: NORTH STAR AVENUE POLARIS HOUSE city: SWINDON postcode: SN2 1FL contact info Titolo: Ms. Nome: Elizabeth Cognome: Cutler Email: send email Telefono: +44 122 340 2357 Fax: +44 122 341 2515
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	172˙740 €
EC contributo	172˙740 €
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-2009-IEF
Funding Scheme	MC-IEF
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-10-01   -   2013-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	MEDICAL RESEARCH COUNCIL  Organization address address: NORTH STAR AVENUE POLARIS HOUSE city: SWINDON postcode: SN2 1FL contact info Titolo: Ms. Nome: Elizabeth Cognome: Cutler Email: send email Telefono: +44 122 340 2357 Fax: +44 122 341 2515	UK (SWINDON)	coordinator	172˙740.80

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 Obiettivo del progetto (Objective)

'Metazoa evolved homogametic and heterogametic sexes. In heterogametic sexes one of the two sex chromosomes underwent loss of essential genes and molecular mechanisms evolved to compensate for this loss. In fruit flies, males up-regulate the transcription levels of many genes on the only sex chromosome by 2-fold. This effect is associated with acetylation of H4K16 mediated by MOF, the catalytic subunit of the Dosage Compensation Complex (DCC). The DCC can be narrowed down to the MSL1-MSL3-MOF complex (MW=280kDa). MSL1 and MSL3 enhance MOF catalysis, probably by inducing a conformational change in the enzyme, and guide its substrate recognition, by an unknown mechanism. To answer these questions I propose to solve the three-dimensional structure of the MOF-MSL1-MSL3 complex and compare it to the structure of MOF alone. Moreover, I propose to elucidate the three-dimensional structure of the MSL1-MSL3-MOF/nucleosomes complex (MW=400kDa) using a combination of X-ray crystallography and electron microscopy. MOF belongs to the family of MYST acetyl-transferases involved in many nuclear processes such as DNA damage response and transcription. The structure of MSL1-MSL3-MOF bound to nucleosomes will reveal how MYST enzymes function. More in general, the DCC can be regarded as a powerful molecular tool to understand how chromatin-remodelling complexes recognize nucleosomes and modify them.'

Introduzione (Teaser)

Accessibility of DNA in chromatin is controlled by protein complexes interacting with chromatin fibres. Resolving the structure of these regulatory complexes is necessary for understanding the very basics of chromatin regulation.