MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
- Howard Hughes Medical Institute, The Rockefeller University, United States
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- La Jolla Institute For Allergy and Immunology, United States
- Howard Hughes Medical Institute, University of California, Berkeley, United States
Abstract
Methyl-CpG-binding-Protein 2 (MeCP2) is an abundant nuclear protein highly enriched in neurons. Here we report live-cell single-molecule imaging studies of the kinetic features of mouse MeCP2 at high spatial-temporal resolution. MeCP2 displays dynamic features that are distinct from both highly mobile transcription factors and immobile histones. Stable binding of MeCP2 in living neurons requires its methyl-binding domain and is sensitive to DNA modification levels. Diffusion of unbound MeCP2 is strongly constrained by weak, transient interactions mediated primarily by its AT-hook domains, and varies with the level of chromatin compaction and cell type. These findings extend previous studies of the role of the MeCP2 MBD in high affinity DNA binding to living neurons, and identify a new role for its AT-hooks domains as critical determinants of its kinetic behavior. They suggest that limited nuclear diffusion of MeCP2 in live neurons contributes to its local impact on chromatin structure and gene expression.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Elitsa I Stoyanova
Funding
Howard Hughes Medical Institute
- Nathaniel Heintz
Howard Hughes Medical Institute
- Zhe Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Job Dekker, University of Massachusetts Medical School, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (# 16944) of the Rockefeller University. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Rockefeller University (OLAW assurance # #A3081-01).
Version history
- Received: August 28, 2019
- Accepted: December 22, 2019
- Accepted Manuscript published: December 23, 2019 (version 1)
- Version of Record published: January 13, 2020 (version 2)
Copyright
© 2019, Piccolo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
eLife 8:e51449.
https://doi.org/10.7554/eLife.51449
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