Summary
The ability of cells to specialize and maintain their identity through multiple cell divisions is critical for development, tissue renewal and diseases avoidance. A key frontier is therefore to understand how genome organization and function is inherited to daughter cells. EPICHS targets a new paradigm for how epigenetic information is propagated, in which communication between the 2D epigenome and 3D genome organization maintains cellular identity. Inheritance of epigenetic states involves the copying of modifications on DNA and histones in cis on replicated DNA. However, this model lacks a spatial dimension, integrating that similar chromatin types separate spatially in the nucleus and replicates in a coordinated fashion. DNA replication severely disrupts the 2D epigenome, but it is unknown how replication locally impact on 3D organization and how spatial context shapes replication of the epigenome. EPICHS will interrogate chromosome replication across scales; we will develop new technology to address the interplay between 2D and 3D epigenome in epigenetic inheritance across replication. We will combine these technologies with machine learning, proteomics and fast-acting degrons to manipulate chromatin replication. Functionally, we will explore replication-induced 2D/3D dynamics and inheritance mechanisms in regulation of transcription and stem cell plasticity. Together, this will 1) provide the first knowledge of interdependencies and directionality in propagation of 2D and 3D organization, 2) reveal functions of DNA replication-induced plasticity in cell fate transitions, and 3) unveil spatio-temporal epigenetic mechanisms and their synergy with cis-based memory in maintaining cell identity.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101142230 |
| Start date: | 01-10-2024 |
| End date: | 30-09-2029 |
| Total budget - Public funding: | 2 500 000,00 Euro - 2 500 000,00 Euro |
Cordis data
Original description
The ability of cells to specialize and maintain their identity through multiple cell divisions is critical for development, tissue renewal and diseases avoidance. A key frontier is therefore to understand how genome organization and function is inherited to daughter cells. EPICHS targets a new paradigm for how epigenetic information is propagated, in which communication between the 2D epigenome and 3D genome organization maintains cellular identity. Inheritance of epigenetic states involves the copying of modifications on DNA and histones in cis on replicated DNA. However, this model lacks a spatial dimension, integrating that similar chromatin types separate spatially in the nucleus and replicates in a coordinated fashion. DNA replication severely disrupts the 2D epigenome, but it is unknown how replication locally impact on 3D organization and how spatial context shapes replication of the epigenome. EPICHS will interrogate chromosome replication across scales; we will develop new technology to address the interplay between 2D and 3D epigenome in epigenetic inheritance across replication. We will combine these technologies with machine learning, proteomics and fast-acting degrons to manipulate chromatin replication. Functionally, we will explore replication-induced 2D/3D dynamics and inheritance mechanisms in regulation of transcription and stem cell plasticity. Together, this will 1) provide the first knowledge of interdependencies and directionality in propagation of 2D and 3D organization, 2) reveal functions of DNA replication-induced plasticity in cell fate transitions, and 3) unveil spatio-temporal epigenetic mechanisms and their synergy with cis-based memory in maintaining cell identity.Status
SIGNEDCall topic
ERC-2023-ADGUpdate Date
03-10-2024
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