Role of epigenetic mechanisms in random X chromosome inactivation ex vivo and in vivo. (360G-Wellcome-201369_Z_16_Z)

£250,000

Developmental progression is linked to accumulation of epigenetic information mainly in the form of chemical modifications of the chromatin. One of the most striking examples of that is random X chromosome inactivation (XCI) in female mammalian embryos. This process is dependent on coating of one X chromosome by a long non-coding RNA, Xist. This in turn promotes rapid and dramatic remodelling of the chromatin. The functional relevance and exact spatio-temporal dynamics of this process remains elusive. Here I propose to address these questions by using an integrated approach. Firstly I will use an ex vivo embryo culture system to monitor the dynamics of XCI. I will further integrate that information with single cell and population based epigenomic to generate in vivo and in vitro datasets accounting to a roadmap for XCI. I aim at identifying the initial stages of epigenetic programming leading to transcriptional repression as well as genomic loci involved in nucleating these changes. I will finally address the functional relevance of X chromosome epigenetic programming by using gene knockout models and genome-wide single cell transcriptomics approach. Such work will have wide-raging implications beyond the field of XCI and can be extrapolated into other epigenetic regulatory mechanisms.

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Grant Details

Amount Awarded 250000
Applicant Surname Zylicz
Approval Committee Basic Science Interview Committee
Award Date 2016-04-19T00:00:00+00:00
Financial Year 2015/16
Grant Programme: Title Sir Henry Wellcome Postdoctoral Fellowship
Internal ID 201369/Z/16/Z
Lead Applicant Dr Jan Zylicz
Partnership Value 250000
Planned Dates: End Date 2020-03-15T00:00:00+00:00
Planned Dates: Start Date 2016-07-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof William Harris