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Updated: Sep 16, 2025

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Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome
Published on: March 2, 2018
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Retrospective and multifactorial single-cell profiling reveals sequential chromatin reorganization during X
Samy Kefalopoulou1,2, Pim M J Rullens1,2,3, Kim L de Luca1,2
1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, Utrecht, The Netherlands.
Nature Cell Biology
|July 10, 2025
Summary
Researchers developed Dam&ChIC, a novel method for single-cell chromatin profiling. This technique captures both past and present chromatin states, revealing the temporal order of gene regulation events.
Area of Science:
- Molecular Biology
- Epigenetics
- Genomics
Background:
- Gene expression is regulated by chromatin organization.
- Coordinated gene regulation mechanisms are not well understood.
Purpose of the Study:
- To develop a method for retrospective and multifactorial chromatin profiling in single cells.
- To investigate the temporal order of gene regulatory events.
Main Methods:
- Developed Dam&ChIC, a method combining m6A chromatin labeling for past states and antibody-mediated readout for present states.
- Applied Dam&ChIC to track lamina-associated domain inheritance and analyze X chromosome inactivation.
Main Results:
- Dam&ChIC provides retrospective single-cell chromatin data.
- The method successfully disentangled the temporal order of chromatin remodeling during X chromosome inactivation.
- Observed genome-lamina detachment preceding Polycomb spreading on the inactive X chromosome.
Conclusions:
- Dam&ChIC offers high resolution and versatility for multifactorial chromatin profiling.
- The method is instrumental in understanding the interconnectivity and order of gene regulatory events.
- Provides insights into cell-state changes during development.
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