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Dynamics of modified chromatin domains

Dynamics of modified chromatin domains

Objective

Cellular identity is defined by complex patterns of DNA and histone modifications, which partition our chromosomes and determine how cells interpret the genetic information. For cells to remember who they are, these modifications have to be tightly regulated over time and through cell division. Loss of cellular identity promotes different types of disease including neurological disorders and cancer.
Histone modifications can spread along chromatin and can be transmitted through cell division, giving rise to chromatin position effects and cellular memory. However, the underlying molecular mechanisms are not understood. In particular, we do not know how the size and stability of modified domains is controlled, and we currently lack techniques to study these processes in real-time.
Here, I propose to develop the single-molecule ‘chromatin curtains’ platform to directly visualize spreading and maintenance of histone methylation in a reconstituted system and to compare the resulting domains to those found on individual chromatin fibers isolated from cells. In a complementary approach, I will devise and set up a tunable synthetic circuit that installs and reinforces orthogonal epigenetic modifications in living cells to define the functional modules that are necessary and sufficient for chromatin position effects and cellular memory.
My project combines molecular biophysics with synthetic biology to elucidate the fundamental principles that govern the dynamics of histone modifications to establish and preserve cellular identity. The chromatin curtains platform I will develop complements sequencing-based methods and will make it for the first time possible to directly assess the dynamics of histone modification patterns on single chromatin fibers under native conditions. I anticipate that the insights gained in my project will aid in the design of future strategies to control histone modifications in disease.
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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

Address

Rue Michel Ange 3
75794 Paris

France

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 447 860

Beneficiaries (1)

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CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France

EU Contribution

€ 1 447 860

Project information

Grant agreement ID: 804023

Status

Ongoing project

  • Start date

    1 July 2019

  • End date

    30 June 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 447 860

  • EU contribution

    € 1 447 860

Hosted by:

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France