Evidence map›Paper›PMID 39689710›Full record

ArticleNeuron2025

Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis.

Sameer S Bajikar, Jian Zhou, Ryan O'Hara, Harini P Tirumala, Mark A Durham, Alexander J Trostle, Michelle Dias, Yingyao Shao, Hu Chen, Wei Wang and 5 more

Abstract read
In one paragraph

Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
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  5. Article
  6. Review
  7. Article
  8. Modulating alternative splicing ofScience translational medicine · 2026
    Article
  9. Article
  10. Article
  11. The CaInternational journal of molecular sciences · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Biomolecules · 2025
    Article
  17. Article
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Sameer S BajikarDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Jian ZhouDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Ryan O'HaraCecil H. and Ida Green Center for Reproductive Biology Sciences, Children's Medical Center Research Institute, Department of Obstetrics and Gynecology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Harini P TirumalaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Mark A DurhamJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.
Alexander J TrostleJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Michelle DiasJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Yingyao ShaoJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Hu ChenJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Wei WangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Hari Krishna YalamanchiliJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Ying-Wooi WanDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Laura A BanaszynskiCecil H. and Ida Green Center for Reproductive Biology Sciences, Children's Medical Center Research Institute, Department of Obstetrics and Gynecology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Zhandong LiuJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Huda Y ZoghbiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: hzoghbi@bcm.edu.

Funding

Steps towards a paternal gene activation therapy for Angelman syndromeU54HD083092 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI ARENKIEL, BENJAMIN R, NELSON, DAVID LOREN · 2014 to 2019
$7.8M
MOLECULAR PATHOGENESIS STUDIES OF RETT SYNDROMER01NS057819 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI ZOGHBI, HUDA Y · 2006 to 2025
$7.5M
Chromatin Dynamics and Genome RegulationR35GM124958 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI Laura Banaszynski · 2017 to 2026
$4.4M
Mechanisms of p300 Activation During Pluripotency and Differentiation.R01HD109239 · NICHD · UT SOUTHWESTERN MEDICAL CENTER · PI Laura Banaszynski · 2022 to 2026
$2.1M
The role of Tcf20 in activity-dependent inhibitory signaling and autism spectrum disorder pathogenesisR00NS129963 · NINDS · EMORY UNIVERSITY · PI Jian Zhou · 2024 to 2026
$725k
Investigating the role of Growth-differentiation factor 11 in neurodevelopmental and MECP2-related disordersF32HD100048 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI BAJIKAR, SAMEER · 2019 to 2021
$168k
The role of Tcf20 in activity-dependent inhibitory signaling and autism spectrum disorder pathogenesisK99NS129963 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI ZHOU, JIAN · 2023 to 2023
$122k
Howard Hughes Medical InstituteNICHD NIH HHS F32 HD100048NICHD NIH HHS R01 HD109239NICHD NIH HHS U54 HD083092NIGMS NIH HHS R35 GM124958NINDS NIH HHS K99 NS129963NINDS NIH HHS R00 NS129963NINDS NIH HHS R01 NS057819
6 · The paper itself

Abstract

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis. We performed time series transcriptional, chromatin, and phenotypic analyses of the hippocampus to determine the immediate consequences of MeCP2 loss and the cascade of pathogenesis. We find that loss of MeCP2 causes immediate and bidirectional progressive dysregulation of the transcriptome. To understand what drives gene downregulation, we profiled genome-wide histone modifications and found that a decrease in histone H3 acetylation (ac) at downregulated genes is among the earliest molecular changes occurring well before any measurable deficiencies in electrophysiology and neurological function. These data reveal a molecular cascade that drives disease independent of any developmental contributions or secondary pathogenesis.

Indexed as

ChromatinHippocampusMethyl-CpG-Binding Protein 2Nervous System DiseasesRett SyndromeTranscription, GeneticAcetylationAnimalsFemaleHistonesMaleMiceMice, Inbred C57BLMice, KnockoutTranscriptomeChromatinHistonesMecp2 protein, mouseMethyl-CpG-Binding Protein 2acute dosage sensitivityphenotypic trajectoryRett syndrometime series transcriptomics

Identifiers

PMID39689710
PMCPMC11802321

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.