Innovating Works

SCORA

Financiado
A systematic characterization of human regulatory architectures and their determ...
A systematic characterization of human regulatory architectures and their determinants of regulatory activity Enhancers control the correct spatio-temporal activation of gene expression. A comprehensive characterization of the properties and regulatory activities of enhancers as well as their target genes is therefore crucial to understan... Enhancers control the correct spatio-temporal activation of gene expression. A comprehensive characterization of the properties and regulatory activities of enhancers as well as their target genes is therefore crucial to understand the regulation and dysregulation of differentiation, homeostasis and cell type specificity. Genome-wide chromatin assays have provided insight into the properties and complex architectures by which enhancers regulate genes, but the understanding of their mechanisms is fragmented and their regulatory targets are mostly unknown. Several factors may confound the inference and interpretation of regulatory enhancer activity. There are likely many kinds of regulatory architectures with distinct levels of output and flexibility. Despite this, most state-of-the-art genome-wide studies only consider a single model. In addition, chromatin-based analysis alone does not provide clear insight into function or activity. This project aims to systematically characterize enhancer architectures and delineate what determines their: (1) restricted spatio-temporal activity; (2) robustness to regulatory genetic variation; and (3) dynamic activities over time. My work has shown enhancer transcription to be the most accurate classifier of enhancer activity to date. This data permits unprecedented modeling of regulatory architectures via enhancer-promoter co-expression linking. Careful computational analysis of such data from appropriate experimental systems has a great potential for distinguishing the different modes of regulation and their functional impact. The outcomes have great potential for providing us with new insights into mechanisms of transcriptional regulation. The results will be particularly relevant to interpretation of regulatory genetic variations. Ultimately, knowing the characteristics and conformations of enhancer architectures will increase our ability to link variation in non-coding DNA to phenotypic outcomes like disease susceptibility. ver más
31/01/2021
UCPH
1M€
Duración del proyecto: 69 meses Fecha Inicio: 2015-04-15
Fecha Fin: 2021-01-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-01-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-StG-2014: ERC Starting Grant
Cerrada hace 10 años
Presupuesto El presupuesto total del proyecto asciende a 1M€
Líder del proyecto
KOBENHAVNS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5