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FUNCTIONS OF CHROMATIN MARKS IN REGULATION OF GENE EXPRESSION

In multicellular organisms, during embryogenesis and tissue homeostasis the differentiation of pluripotent stem cells into a variety of specialized cell types is governed by diverse transcriptional programs, the establishment and... ver más

29/02/2016

IMB

75K€

Presupuesto del proyecto: 75K€

Líder del proyecto

INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2016-02-29 No tenemos la información de la convocatoria

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Líder del proyecto

INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 75K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto In multicellular organisms, during embryogenesis and tissue homeostasis the differentiation of pluripotent stem cells into a variety of specialized cell types is governed by diverse transcriptional programs, the establishment and maintenance of which rely on epigenetic mechanisms, such as chromatin modifications. Over the past years, a large number of post-translational modifications of histones as well as enzymes responsible for either positioning or removal of these marks were characterized. Genome-wide studies mapping the distribution of histone modifications revealed a complex epigenetic landscape on eukaryotic chromosomes. In particular, distinct chromatin signatures were recently associated with enhancer elements, cis-acting DNA sequences inducing transcription from target promoters. However, whether the deposition of specific marks at enhancers is a pre-requisite for their activity or a mere consequence of the recruitment of histone-modifying complexes at their target promoters is an entirely open question. The aim of this proposal is to define the biological significance of histone modifications covering enhancer sequences in vivo. To perform this study we will generate transgenic mice allowing us to target histone-modifying activities at enhancers using a recently introduced technology based on transcription activator–like effectors (TALEs). The developing limb will serve as a model system since several well-defined enhancers are active specifically in this structure. We will validate this approach by assessing changes in histone marks over enhancer sequences in transgenic versus wild type mice. Next, we will determine how such changes affect the transcriptional status of the endogenous target gene of the enhancer by scoring both RNA levels and limb phenotypes. The results of this study are likely to have a major impact on our understanding of chromatin functions in transcriptional regulation.

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