MeCP2 links heterochromatin condensates and neurodevelopmental disease.

Nature
Charles H LiRichard A Young

Abstract

Methyl CpG binding protein 2 (MeCP2) is a key component of constitutive heterochromatin, which is crucial for chromosome maintenance and transcriptional silencing1-3. Mutations in the MECP2 gene cause the progressive neurodevelopmental disorder Rett syndrome3-5, which is associated with severe mental disability and autism-like symptoms that affect girls during early childhood. Although previously thought to be a dense and relatively static structure1,2, heterochromatin is now understood to exhibit properties consistent with a liquid-like condensate6,7. Here we show that MeCP2 is a dynamic component of heterochromatin condensates in cells, and is stimulated by DNA to form liquid-like condensates. MeCP2 contains several domains that contribute to the formation of condensates, and mutations in MECP2 that lead to Rett syndrome disrupt the ability of MeCP2 to form condensates. Condensates formed by MeCP2 selectively incorporate and concentrate heterochromatin cofactors rather than components of euchromatic transcriptionally active condensates. We propose that MeCP2 enhances the separation of heterochromatin and euchromatin through its condensate partitioning properties, and that disruption of condensates may be a common consequence ...Continue Reading

References

Apr 4, 2003·Human Mutation·John ChristodoulouBruce Bennetts
Jun 6, 2003·The Journal of Biological Chemistry·Philippe T GeorgelJeffrey C Hansen
Oct 21, 2006·Molecular Cell·Alejandra LoyolaGeneviève Almouzni
Feb 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Emanuela GiacomettiRudolf Jaenisch
May 24, 2007·Bioinformatics·John A Capra, Mona Singh
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
Oct 30, 2012·Cell·Jakob LovénRichard A Young
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jun 19, 2013·Nature Neuroscience·Matthew J LystAdrian Bird
Mar 4, 2015·Nature Reviews. Genetics·Matthew J Lyst, Adrian Bird
Jan 12, 2017·Biophysical Journal·Alex S HolehouseRohit V Pappu
Mar 30, 2017·Proceedings of the National Academy of Sciences of the United States of America·Valdeko KruusveeAtlanta G Cook
Jun 22, 2017·Nature·Amy R StromGary H Karpen
Sep 25, 2017·Science·Yongdae Shin, Clifford P Brangwynne
Oct 12, 2017·Nature·Rebekah TillotsonAdrian Bird
Dec 14, 2017·Nature Reviews. Molecular Cell Biology·Robin C Allshire, Hiten D Madhani
May 10, 2018·Nature Reviews. Neuroscience·Jacque P K IpMriganka Sur
Jun 27, 2018·Journal of Molecular Biology·Simon AlbertiAnthony A Hyman
Jul 26, 2018·Annual Review of Cell and Developmental Biology·Aniek JanssenGary H Karpen
Aug 10, 2019·Molecular Cell·Krishna ShrinivasArup K Chakraborty
Sep 24, 2019·Cell·Bryan A GibsonMichael K Rosen
Sep 30, 2019·Molecular Cell·Alicia V ZamudioRichard A Young
Jun 20, 2020·Science·Isaac A KleinRichard A Young

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Citations

Jan 9, 2021·Cancer Cell·Ann BoijaRichard A Young
Dec 18, 2020·Cell·Jonathan E HenningerRichard A Young
Jan 9, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·John B Vincent, Juan Ausió
Nov 19, 2020·Cells·Sergey V Razin, Sergey V Ulianov
Feb 9, 2021·Frontiers in Genetics·Katrina V GoodJuan Ausió
Dec 12, 2020·Genome Génome / Conseil National De Recherches Canada·Hilmar Strickfaden
Mar 10, 2021·Epigenomics·Yui Imaizumi, Robert Feil
May 11, 2021·Frontiers in Genetics·Osman Sharifi, Dag H Yasui
Jul 17, 2021·Journal of Molecular Biology·Wei Li, Hao Jiang
Jul 27, 2021·DNA Repair·Vincent Spegg, Matthias Altmeyer
Aug 4, 2021·Nature Reviews. Molecular Cell Biology·Prashant BhatMitchell Guttman
Feb 28, 2021·Journal of Neurochemistry·Santosh R D'Mello
Sep 19, 2021·Molecular Neurodegeneration·Artemis IatrouYanling Wang
May 19, 2021·Cold Spring Harbor Perspectives in Biology·Feiyue Lu, Timothée Lionnet

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Methods Mentioned

BETA
fluorescence microscopy
PCR
transfection
genotyping
flow cytometry
dissection
Protein Assay
Assay
RNA-seq

Software Mentioned

GraphPad
RSEM
DESeq2
Prism
ENCODE
localCIDER
STAR aligner
PONDR VLS2
Clustal Omega
ZEN Black Edition

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