CORDIS
EU research results

CORDIS

English EN

Dissecting the regulatory logic of poised enhancers

Project information

Grant agreement ID: 862022

Status

Grant agreement signed

  • Start date

    1 September 2020

  • End date

    31 August 2025

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 997 662

  • EU contribution

    € 1 997 662

Hosted by:

UNIVERSIDAD DE CANTABRIA

Spain

Objective

The mechanisms that, despite the noisy and stochastic nature of transcription, enable the specific, precise and robust deployment of developmental gene expression programs are poorly understood. We previously identified Poised Enhancers (PEs) as a conserved set of cis-regulatory elements essential for the induction of major anterior neural genes upon ESC differentiation. Importantly, before becoming active in anterior neural progenitors, PEs are already bookmarked in embryonic stem cells (ESC) with unique chromatin and topological features, including binding by polycomb-group protein complexes (PcG) and pre-formed contacts with their target genes. Here I hypothesize that the competence of pluripotent cells to faithfully execute an anterior neural gene expression program is genetically encoded and dependent on the unique modular composition of PEs, consisting of a cluster of highly conserved transcription factor binding sites (TFBS) and a nearby CpG island (CGI). This modular composition might endow PEs with privileged regulatory properties, whereby the TFBS confer cis-activation capacity, while the CGI bestow permissive chromatin and topological features that boost the PEs regulatory activity and increase transcriptional precision. Furthermore, I hypothesize that, together with architectural proteins, this modular composition dictates the specificity, compatibility and responsiveness between PEs and their target genes. Using ESC as a tractable system and genomic, single-cell/single-allele and genetic engineering methods, we will systematically dissect the contribution of each PE module (i.e. TFBS, CGI) and of different epigenetic (e.g. PcG, DNA methylation) and architectural factors (e.g. Cohesin, CTCF) to the regulatory logic of PEs. By systematically dissecting PEs, our work will illuminate novel and general mechanisms whereby enhancer pre-marking facilitates the precise and specific establishment of gene expression programs during vertebrate embryogenesis.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Host institution

UNIVERSIDAD DE CANTABRIA

Address

Avenida De Los Castros S/N
39005 Santander

Spain

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 997 662

Beneficiaries (1)

UNIVERSIDAD DE CANTABRIA

Spain

EU Contribution

€ 1 997 662

Project information

Grant agreement ID: 862022

Status

Grant agreement signed

  • Start date

    1 September 2020

  • End date

    31 August 2025

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 997 662

  • EU contribution

    € 1 997 662

Hosted by:

UNIVERSIDAD DE CANTABRIA

Spain