Innovating Works

BFU2009-07111

Financiado
REGULACION EPIGENETICA DE LA ESTRUCTURA Y FUNCION DE LA CROMATINA
GENOMIC FUNCTIONS TAKE PLACE IN CHROMATIN, NOT IN NAKED DNA, OVER THE LAST FEW YEARS, WE HAVE BECOME INCREASINGLY AWARE OF THE IMPORTANT CONTRIBUTION OF CHROMATIN TO THE REGULATION OF GENOMIC FUNCTIONS, AS CHANGES IN CHROMATIN STR... GENOMIC FUNCTIONS TAKE PLACE IN CHROMATIN, NOT IN NAKED DNA, OVER THE LAST FEW YEARS, WE HAVE BECOME INCREASINGLY AWARE OF THE IMPORTANT CONTRIBUTION OF CHROMATIN TO THE REGULATION OF GENOMIC FUNCTIONS, AS CHANGES IN CHROMATIN STRUCTURE HAVE BEEN FOUND TO PLAY A FUNDAMENTAL ROLE IN THE REGULATION OF MULTIPLE GENOMIC PROCESSES, FROM GENE EXPRESSION TO CHROMOSOME SEGREGATION AND THE MAINTENANCE OF GENOME INTEGRITY AND STABILITY, FURTHERMORE, INCREASING EVIDENCE INDICATES THAT ALTERATIONS IN CHROMATIN STRUCTURE AND FUNCTIONALITY ARE ON THE BASIS OF MANY HUMAN PATHOLOGIES, INCLUDING SEVERAL TYPES OF CANCER AND SOME BRAIN DISORDERS, OUR CURRENT KNOWLEDGE ABOUT THE REGULATION OF CHROMATIN FUNCTIONS HAS BENEFITTED FROM THE IDENTIFICATION OF COMPONENTS, AND MECHANISMS, THAT COVALENTLY AND STRUCTURALLY MODIFY CHROMATIN, THESE INCLUDE CHROMATIN ASSEMBLY AND REMODELLING COMPLEXES, HISTONE MODIFICATIONS (EG, ACETYLATION, METHYLATION, PHOSPHORYLATION, UBIQUITINATION,¿) AND THE CORRESPONDING ENZYMES (EG, HATS, HDACS, HMTS, HDMS,¿), NON-HISTONE PROTEINS (EG, HP1, PC,¿) THAT RECOGNISE SPECIFIC HISTONE MODIFICATIONS AND CONTRIBUTE TO THE ESTABLISHMENT OF DISTINCT CHROMATIN DOMAINS, HISTONE VARIANTS WHICH LOCALISE TO SPECIFIC CHROMOSOMAL LOCATIONS (EG, CENH3/CENP-A, H3,3, H2A,Z, MACROH2A) AND NON-CODING RNAS THAT MODIFY CHROMATIN STRUCTURE AND REGULATE GENE EXPRESSION, HERE, WE PROPOSE TO FURTHER CHARACTERISE THE COMPONENTS AND MECHANISMS THAT REGULATE CHROMATIN STRUCTURE AND FUNCTION, MORE SPECIFICALLY, BASED ON OUR OWN RECENT RESULTS (PUBLISHED IN LEADING JOURNALS IN THE FIELD), WE PROPOSE TO: (1) ANALYSE THE CONTRIBUTION OF THE CENTROMERIC HISTONE H3 VARIANT, CENH3/CENP-A, TO CENTROMERE FUNCTION, WE AIM TO DETERMINE THE MOLECULAR BASIS OF ITS CONTRIBUTION TO KINETOCHORE ASSEMBLY AND TO CHARACTERISE THE MOLECULAR MECHANISMS RESPONSIBLE FOR ITS SPECIFIC LOCALISATION AT CENTROMERES,(2) ANALYSE THE CONTRIBUTION OF THE CENP-B FAMILY OF CENTROMERIC PROTEINS TO HETEROCHROMATIN FUNCTION AND GENOME INTEGRITY/STABILITY IN THE YEAST SCHIZOSACCHAROMYCES POMBE,(3) FUNCTIONALLY CHARACTERISE THE JMJC+N FAMILY OF HISTONE LYSINE-DEMETHYLASES (KDMS) IN DROSOPHILA, IN PARTICULAR, WE AIM TO DETERMINE THEIR CONTRIBUTION TO THE REGULATION OF GENE EXPRESSION DURING DEVELOPMENT AND TO THE FORMATION/MAINTENANCE OF HETEROCHROMATIN,(4) FUNCTIONALLY CHARACTERISE THE FAMILY OF HP1-PROTEINS IN DROSOPHILA AND, MORE SPECIFICALLY, THE MOLECULAR MECHANISMS OF THEIR CONTRIBUTION TO THE REGULATION OF GENE EXPRESSION DURING DEVELOPMENT,(5) CHARACTERISE THE CONTRIBUTION OF HISTONE H1 TO CHROMATIN STRUCTURE AND FUNCTION IN DROSOPHILA, WE AIM TO DETERMINE ITS SPECIFIC CONTRIBUTION TO THE REGULATION OF GENE EXPRESSION DURING DEVELOPMENT AND DIFFERENTIATION, ITS PATTERN OF POST-TRANSLATIONAL MODIFICATIONS, IN PARTICULAR OF LYSINE-METHYLATION AT THE N-TERMINAL DOMAIN, AND THE FUNCTIONAL CONSEQUENCES OF THESE MODIFICATIONS, CROMATINA\CENTROMERO\TRANSCRIPCION\CENH3\DEMETILASAS\HP1\H1\CENP-B\DROSOPHILA\YEAST ver más
01/01/2009
CSIC
716K€
Perfil tecnológico estimado

Línea de financiación: concedida

El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2009-01-01
Presupuesto El presupuesto total del proyecto asciende a 716K€
Líder del proyecto
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 2-3 552M