DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders

Diana L. Christian; Dennis Y. Wu; Jenna R. Martin; J. Russell Moore; Yiran R. Liu; Adam W. Clemens; Sabin A. Nettles; Nicole M. Kirkland; Thomas Papouin; Cheryl A. Hill; David F. Wozniak; Joseph D. Dougherty; Harrison W. Gabel

doi:10.1016/j.celrep.2020.108416

DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders

Diana L. Christian, Dennis Y. Wu, Jenna R. Martin, J. Russell Moore, Yiran R. Liu, Adam W. Clemens, Sabin A. Nettles, Nicole M. Kirkland, Thomas Papouin, Cheryl A. Hill, David F. Wozniak, Joseph D. Dougherty, Harrison W. Gabel

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31 Scopus citations

Abstract

Christian et al. find that neurodevelopmental disease-associated DNMT3A mutations have shared neuronal DNA methylation deposition deficits. DNMT3A^KO/+ mice display reduced global non-CG DNA methylation, behavior, and growth phenotypes relevant to human disease. Transcriptomic and epigenomic changes in these mice overlap models of Rett syndrome and autism, suggesting convergent pathology.

Original language	English
Article number	108416
Journal	Cell Reports
Volume	33
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2020.108416
State	Published - Nov 24 2020

Keywords

Autism
DNA methylation
DNMT3A
MeCP2
Rett Syndrome
TBRS
cerebral cortex
enhancer
intellectual disability
non-CG methylation

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10.1016/j.celrep.2020.108416

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Christian, D. L., Wu, D. Y., Martin, J. R., Moore, J. R., Liu, Y. R., Clemens, A. W., Nettles, S. A., Kirkland, N. M., Papouin, T., Hill, C. A., Wozniak, D. F., Dougherty, J. D., & Gabel, H. W. (2020). DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders. Cell Reports, 33(8), Article 108416. https://doi.org/10.1016/j.celrep.2020.108416

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title = "DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders",

abstract = "Christian et al. find that neurodevelopmental disease-associated DNMT3A mutations have shared neuronal DNA methylation deposition deficits. DNMT3AKO/+ mice display reduced global non-CG DNA methylation, behavior, and growth phenotypes relevant to human disease. Transcriptomic and epigenomic changes in these mice overlap models of Rett syndrome and autism, suggesting convergent pathology.",

keywords = "Autism, DNA methylation, DNMT3A, MeCP2, Rett Syndrome, TBRS, cerebral cortex, enhancer, intellectual disability, non-CG methylation",

author = "Christian, {Diana L.} and Wu, {Dennis Y.} and Martin, {Jenna R.} and Moore, {J. Russell} and Liu, {Yiran R.} and Clemens, {Adam W.} and Nettles, {Sabin A.} and Kirkland, {Nicole M.} and Thomas Papouin and Hill, {Cheryl A.} and Wozniak, {David F.} and Dougherty, {Joseph D.} and Gabel, {Harrison W.}",

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year = "2020",

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doi = "10.1016/j.celrep.2020.108416",

language = "English",

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Christian, DL, Wu, DY, Martin, JR, Moore, JR, Liu, YR, Clemens, AW, Nettles, SA, Kirkland, NM, Papouin, T, Hill, CA, Wozniak, DF, Dougherty, JD & Gabel, HW 2020, 'DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders', Cell Reports, vol. 33, no. 8, 108416. https://doi.org/10.1016/j.celrep.2020.108416

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T1 - DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders

AU - Christian, Diana L.

AU - Wu, Dennis Y.

AU - Martin, Jenna R.

AU - Moore, J. Russell

AU - Liu, Yiran R.

AU - Clemens, Adam W.

AU - Nettles, Sabin A.

AU - Kirkland, Nicole M.

AU - Papouin, Thomas

AU - Hill, Cheryl A.

AU - Wozniak, David F.

AU - Dougherty, Joseph D.

AU - Gabel, Harrison W.

PY - 2020/11/24

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AB - Christian et al. find that neurodevelopmental disease-associated DNMT3A mutations have shared neuronal DNA methylation deposition deficits. DNMT3AKO/+ mice display reduced global non-CG DNA methylation, behavior, and growth phenotypes relevant to human disease. Transcriptomic and epigenomic changes in these mice overlap models of Rett syndrome and autism, suggesting convergent pathology.

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KW - DNA methylation

KW - DNMT3A

KW - MeCP2

KW - Rett Syndrome

KW - TBRS

KW - cerebral cortex

KW - enhancer

KW - intellectual disability

KW - non-CG methylation

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SN - 2211-1247

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JO - Cell Reports

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ER -

DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders

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