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Cited by 225Genetics and Neurodevelopmental DisordersGenomics and Rare DiseasesGenetic Neurodegenerative Diseases

An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders

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Baker, Steven Andrew, Chen, Lin, Wilkins, Angela Dawn, Yu, Peng, Lichtarge, Olivier, Zoghbi, Huda Yahya·2013·Cell
DOI 10.1016/j.cell.2013.01.038PMC PMC3641682
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Abstract

Mutations in the X-linked MECP2 cause Rett syndrome, a devastating neurological disorder typified by a period of apparently normal development followed by loss of cognitive and psychomotor skills. Data from rare male patients suggest symptom onset and severity can be influenced by the location of the mutation, with amino acids 270 and 273 marking the difference between neonatal encephalopathy and death, on the one hand, and survival with deficits on the other. We therefore generated two mouse models expressing either MeCP2-R270X or MeCP2-G273X. The mice developed phenotypes at strikingly different rates and showed differential ATRX nuclear localization within the nervous system, over time, coinciding with phenotypic progression. We discovered that MeCP2 contains three AT-hook-like domains over a stretch of 250 amino acids, like HMGA DNA-bending proteins; one conserved AT-hook is disrupted in MeCP2-R270X, lending further support to the notion that one of MeCP2's key functions is to alter chromatin structure.

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  • MeCP2 may also facilitate transcriptional activation, chromatin compaction and mRNA splicing, while interacting with other regulatory proteins.

    “However, MeCP2 may also facilitate transcriptional activation [77], chromatin compaction [78,79] and mRNA splicing [80,81], while also interacting with a host of other regulatory proteins involved in a variety of molecular pathways [81–84].”

    From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [79]

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Research works printed but not linked: 39

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Cited by

Sorted by citations

Authors
Baker, S. A., Chen, L., Wilkins, A. D., Yu, P., Lichtarge, O., & Zoghbi, H. Y.
Affiliations
  • Baylor College of Medicine (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Zoghbi, Huda Yahya
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2013-02
Volume
152
Issue
5
Pages
984-996
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2013.01.038
PMC
PMC3641682
OpenAlex
W2001420461
Cited by
225
References
4
Citations by year
2026: 8 · 2025: 5 · 2024: 13 · 2023: 9 · 2022: 12 · 2021: 17 · 2020: 15 · 2019: 14 · 2018: 24 · 2017: 18 · 2016: 21 · 2015: 21 · 2014: 22 · 2013: 19
FWCI
18.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of General Medical Sciences (R01GM079656)
  • National Institute of Neurological Disorders and Stroke (F30NS066527, NS053862, P01NS053862, R01NS057819)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 024064, P30HD024064)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
Rett syndrome, MeCP2, mouse model, clinical course, neonatal encephalopathy, chromatin structure, X-linked disorders, mutation location
MeSH terms
X-linked Nuclear Protein, Amino Acid Sequence, Animals, Disease Models, Animal, DNA Helicases, Female, Heterochromatin, Male, Mice, Transgenic, Molecular Sequence Data, Nuclear Proteins, Transcription, Genetic, Rett Syndrome, Sequence Alignment, Protein Structure, Tertiary, Mice, Knockout, Mice, Methyl-CpG-Binding Protein 2

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