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Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits.
Cell Rep. 2020 Jun 30; 31(13):107838.CR

Abstract

ATRX gene mutations have been identified in syndromic and non-syndromic intellectual disabilities in humans. ATRX is known to maintain genomic stability in neuroprogenitor cells, but its function in differentiated neurons and memory processes remains largely unresolved. Here, we show that the deletion of neuronal Atrx in mice leads to distinct hippocampal structural defects, fewer presynaptic vesicles, and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. We identify male-specific impairments in long-term contextual memory and in synaptic gene expression, linked to altered miR-137 levels. We show that ATRX directly binds to the miR-137 locus and that the enrichment of the suppressive histone mark H3K27me3 is significantly reduced upon the loss of ATRX. We conclude that the ablation of ATRX in excitatory forebrain neurons leads to sexually dimorphic effects on miR-137 expression and on spatial memory, identifying a potential therapeutic target for neurological defects caused by ATRX dysfunction.

Authors+Show Affiliations

Children's Health Research Institute, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Biochemistry, Western University, London, ON, Canada.Department of Paediatrics, Western University, London, ON, Canada; PERFORM Centre, Concordia University, Montreal, QC, Canada.Children's Health Research Institute, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada.Children's Health Research Institute, London, ON, Canada; Department of Paediatrics, Western University, London, ON, Canada; Department of Anatomy & Cell Biology, Western University, London, ON, Canada.Children's Health Research Institute, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Anatomy & Cell Biology, Western University, London, ON, Canada.Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada.Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada; Wellcome Centre for Integrative Neuroimaging, The University of Oxford, Oxford, UK.Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, The University of Toronto, Toronto, ON, Canada; Wellcome Centre for Integrative Neuroimaging, The University of Oxford, Oxford, UK.Children's Health Research Institute, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Paediatrics, Western University, London, ON, Canada; Department of Anatomy & Cell Biology, Western University, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada. Electronic address: nberube@uwo.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32610139

Citation

Tamming, Renee J., et al. "Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits." Cell Reports, vol. 31, no. 13, 2020, p. 107838.
Tamming RJ, Dumeaux V, Jiang Y, et al. Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits. Cell Rep. 2020;31(13):107838.
Tamming, R. J., Dumeaux, V., Jiang, Y., Shafiq, S., Langlois, L., Ellegood, J., Qiu, L. R., Lerch, J. P., & Bérubé, N. G. (2020). Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits. Cell Reports, 31(13), 107838. https://doi.org/10.1016/j.celrep.2020.107838
Tamming RJ, et al. Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits. Cell Rep. 2020 Jun 30;31(13):107838. PubMed PMID: 32610139.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits. AU - Tamming,Renee J, AU - Dumeaux,Vanessa, AU - Jiang,Yan, AU - Shafiq,Sarfraz, AU - Langlois,Luana, AU - Ellegood,Jacob, AU - Qiu,Lily R, AU - Lerch,Jason P, AU - Bérubé,Nathalie G, PY - 2019/04/18/received PY - 2020/04/13/revised PY - 2020/06/08/accepted PY - 2020/7/2/entrez PY - 2020/7/2/pubmed PY - 2020/7/2/medline KW - ATRX KW - H3K27me3 KW - chromatin KW - hippocampus KW - intellectual disability KW - long-term spatial memory KW - miR-137 KW - presynaptic vesicles KW - sex differences KW - synapse SP - 107838 EP - 107838 JF - Cell reports JO - Cell Rep VL - 31 IS - 13 N2 - ATRX gene mutations have been identified in syndromic and non-syndromic intellectual disabilities in humans. ATRX is known to maintain genomic stability in neuroprogenitor cells, but its function in differentiated neurons and memory processes remains largely unresolved. Here, we show that the deletion of neuronal Atrx in mice leads to distinct hippocampal structural defects, fewer presynaptic vesicles, and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. We identify male-specific impairments in long-term contextual memory and in synaptic gene expression, linked to altered miR-137 levels. We show that ATRX directly binds to the miR-137 locus and that the enrichment of the suppressive histone mark H3K27me3 is significantly reduced upon the loss of ATRX. We conclude that the ablation of ATRX in excitatory forebrain neurons leads to sexually dimorphic effects on miR-137 expression and on spatial memory, identifying a potential therapeutic target for neurological defects caused by ATRX dysfunction. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/32610139/Atrx_Deletion_in_Neurons_Leads_to_Sexually_Dimorphic_Dysregulation_of_miR-137_and_Spatial_Learning_and_Memory_Deficits L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(20)30819-6 DB - PRIME DP - Unbound Medicine ER -
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