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HISTONEMEMORY SIGNED

New and Old Histones in Epigenetic Cell Memory

Total Cost €

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EC-Contrib. €

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Project "HISTONEMEMORY" data sheet

The following table provides information about the project.

Coordinator
KOBENHAVNS UNIVERSITET 

Organization address
address: NORREGADE 10
city: KOBENHAVN
postcode: 1165
website: www.ku.dk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Denmark [DK]
 Total cost 1˙999˙750 €
 EC max contribution 1˙999˙750 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-05-01   to  2022-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KOBENHAVNS UNIVERSITET DK (KOBENHAVN) coordinator 1˙999˙750.00

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 Project objective

Cell type specific organization of DNA into chromatin is an important determinant of gene expression and cell identity. During cell division, epigenetic information in chromatin must be transmitted to daughter cells in order to maintain cell identity or commit to a developmental program. However, it remains unknown how epigenetic states are inherited during cell division. Elucidating molecular mechanisms underlying epigenetic cell memory thus represents a major challenge in biology critical to understand development and disease.

Chromatin undergoes genome-wide disruption during DNA replication and histone marks are diluted 2-fold due to new histone deposition. Yet, how this impacts on establishment and maintenance of gene expression programs is not known. I hypothesize that chromatin replication represents a critical window for epigenetic cell memory and cell fate decisions, and predict that three histone-based processes play critical roles in guarding cell identity: 1) new histone deposition to regulate nucleosome occupancy and transcription factor (TF) binding, 2) accurate transmission of old modified histones by dedicated recycling machinery, and 3) recruitment of regulatory proteins to new and old histones to direct epigenome maintenance. To dissect these events mechanistically and test causal roles in cell fate decisions, I propose a research program integrating explorative proteomics and histone chaperone structure-function analysis with stem cell biology and new cutting-edge genomic tools developed by my research group.

The proposed research will 1) identify novel mechanisms of histone chaperoning and deposition specific to new and old histones, 2) reveal how nucleosome assembly govern TF binding during DNA replication, and 3) address the significance of old histone recycling and new histone deposition for pluripotency and commitment. This will provide a major advance in understanding the molecular mechanisms that govern epigenetic cell memory.

 Publications

year authors and title journal last update
List of publications.
2018 Sung-Bau Lee, Sandra Segura-Bayona, Marina Villamor-Payà, Giulia Saredi, Matthew A. M. Todd, Camille Stephan-Otto Attolini, Ting-Yu Chang, Travis H. Stracker, Anja Groth
Tousled-like kinases stabilize replication forks and show synthetic lethality with checkpoint and PARP inhibitors
published pages: eaat4985, ISSN: 2375-2548, DOI: 10.1126/sciadv.aat4985
Science Advances 4/8 2020-01-30
2019 Kathleen R. Stewart-Morgan, Nazaret Reverón-Gómez, Anja Groth
Transcription Restart Establishes Chromatin Accessibility after DNA Replication
published pages: 284-297.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.04.033
Molecular Cell 75/2 2020-01-30
2019 Kyosuke Nakamura, Giulia Saredi, Jordan R. Becker, Benjamin M. Foster, Nhuong V. Nguyen, Tracey E. Beyer, Laura C. Cesa, Peter A. Faull, Saulius Lukauskas, Thomas Frimurer, J. Ross Chapman, Till Bartke, Anja Groth
H4K20me0 recognition by BRCA1–BARD1 directs homologous recombination to sister chromatids
published pages: 311-318, ISSN: 1465-7392, DOI: 10.1038/s41556-019-0282-9
Nature Cell Biology 21/3 2020-01-30
2018 Nazaret Reverón-Gómez, Cristina González-Aguilera, Kathleen R. Stewart-Morgan, Nataliya Petryk, Valentin Flury, Simona Graziano, Jens Vilstrup Johansen, Janus Schou Jakobsen, Constance Alabert, Anja Groth
Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication
published pages: 239-249.e5, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.08.010
Molecular Cell 72/2 2020-01-30
2018 Nataliya Petryk, Maria Dalby, Alice Wenger, Caroline B. Stromme, Anne Strandsby, Robin Andersson, Anja Groth
MCM2 promotes symmetric inheritance of modified histones during DNA replication
published pages: 1389-1392, ISSN: 0036-8075, DOI: 10.1126/science.aau0294
Science 361/6409 2019-04-18

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