Epigenomic analysis of Alzheimer's disease brains reveals diminished CTCF binding on genes involved in synaptic organization.
Alzheimer's disease
CTCF
Chromatin organization
Epigenetics
Histone acetylation
Synaptic genes
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
06
02
2023
revised:
31
05
2023
accepted:
01
06
2023
medline:
7
8
2023
pubmed:
12
6
2023
entrez:
11
6
2023
Statut:
ppublish
Résumé
Epigenetic aberrations are suggested to play an important role in transcriptional alterations in Alzheimer's disease (AD). One of the key mechanisms of epigenetic regulation of gene expression is through the dynamic organization of chromatin structure via the master genome architecture protein, CCCTC-binding factor (CTCF). By forming chromatin loops, CTCF can influence gene transcription in a complex manner. To find out whether genome-wide DNA binding sites for CTCF are altered in AD, we compared CTCF chromatin immunoprecipitation sequencing (ChIP-Seq) data from frontal cortex of human AD patients and normal controls (n = 9 pairs, all females). We have revealed that CTCF-binding affinity on many genes is significantly reduced in AD patients, and these genes are enriched in synaptic organization, cell adhesion, and actin cytoskeleton, including synaptic scaffolding molecules and receptors, such as SHANK2, HOMER1, NRXN1, CNTNAP2 and GRIN2A, and protocadherin (PCDH) and cadherin (CDH) family members. By comparing transcriptomic data from AD patients, we have discovered that many of the synaptic and adhesion genes with reduced CTCF binding in AD are significantly reduced in their mRNA expression. Moreover, a significant overlap of genes with the diminished CTCF binding and the reduced H3K27ac is identified in AD, with the common genes enriched in synaptic organization. These data suggest that the CTCF-controlled 3D chromatin organization is perturbed in AD, which may be linked to the diminished expression of target genes, probably through changes in histone modification.
Identifiants
pubmed: 37302762
pii: S0969-9961(23)00207-3
doi: 10.1016/j.nbd.2023.106192
pmc: PMC10519202
mid: NIHMS1931430
pii:
doi:
Substances chimiques
CCCTC-Binding Factor
0
Chromatin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
106192Subventions
Organisme : NIA NIH HHS
ID : R01 AG064656
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG079797
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
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