Cargando…

MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions

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 mobi...

Descripción completa

Detalles Bibliográficos
Autores principales: Piccolo, Francesco M, Liu, Zhe, Dong, Peng, Hsu, Ching-Lung, Stoyanova, Elitsa I, Rao, Anjana, Tjian, Robert, Heintz, Nathaniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957317/
https://www.ncbi.nlm.nih.gov/pubmed/31868585
http://dx.doi.org/10.7554/eLife.51449
_version_ 1783487293982507008
author Piccolo, Francesco M
Liu, Zhe
Dong, Peng
Hsu, Ching-Lung
Stoyanova, Elitsa I
Rao, Anjana
Tjian, Robert
Heintz, Nathaniel
author_facet Piccolo, Francesco M
Liu, Zhe
Dong, Peng
Hsu, Ching-Lung
Stoyanova, Elitsa I
Rao, Anjana
Tjian, Robert
Heintz, Nathaniel
author_sort Piccolo, Francesco M
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6957317
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-69573172020-01-15 MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions Piccolo, Francesco M Liu, Zhe Dong, Peng Hsu, Ching-Lung Stoyanova, Elitsa I Rao, Anjana Tjian, Robert Heintz, Nathaniel eLife Neuroscience 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. eLife Sciences Publications, Ltd 2019-12-23 /pmc/articles/PMC6957317/ /pubmed/31868585 http://dx.doi.org/10.7554/eLife.51449 Text en © 2019, Piccolo et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Piccolo, Francesco M
Liu, Zhe
Dong, Peng
Hsu, Ching-Lung
Stoyanova, Elitsa I
Rao, Anjana
Tjian, Robert
Heintz, Nathaniel
MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
title MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
title_full MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
title_fullStr MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
title_full_unstemmed MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
title_short MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
title_sort mecp2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957317/
https://www.ncbi.nlm.nih.gov/pubmed/31868585
http://dx.doi.org/10.7554/eLife.51449
work_keys_str_mv AT piccolofrancescom mecp2nucleardynamicsinliveneuronsresultsfromlowandhighaffinitychromatininteractions
AT liuzhe mecp2nucleardynamicsinliveneuronsresultsfromlowandhighaffinitychromatininteractions
AT dongpeng mecp2nucleardynamicsinliveneuronsresultsfromlowandhighaffinitychromatininteractions
AT hsuchinglung mecp2nucleardynamicsinliveneuronsresultsfromlowandhighaffinitychromatininteractions
AT stoyanovaelitsai mecp2nucleardynamicsinliveneuronsresultsfromlowandhighaffinitychromatininteractions
AT raoanjana mecp2nucleardynamicsinliveneuronsresultsfromlowandhighaffinitychromatininteractions
AT tjianrobert mecp2nucleardynamicsinliveneuronsresultsfromlowandhighaffinitychromatininteractions
AT heintznathaniel mecp2nucleardynamicsinliveneuronsresultsfromlowandhighaffinitychromatininteractions