TY - JOUR
T1 - Promoter DNA hypermethylation – Implications for Alzheimer's disease
AU - Liu, Yiyuan
AU - Wang, Minghui
AU - Marcora, Edoardo M.
AU - Zhang, Bin
AU - Goate, Alison M.
N1 - Funding Information:
This work was supported by the grants from National Institutes of Health/National Institute on Aging ( U01AG049508 , U01AG052411 , R01AG046170 , RF1AG054014 , RF1AG057440 , R01AG057907 ). The authors would like to thank Dr Julia TCW for editing the paper.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/10/15
Y1 - 2019/10/15
N2 - Recent methylome-wide association studies (MWAS) in humans have solidified the concept that aberrant DNA methylation is associated with Alzheimer's disease (AD). We summarize these findings to improve the understanding of mechanisms governing DNA methylation pertinent to transcriptional regulation, with an emphasis of AD-associated promoter DNA hypermethylation, which establishes an epigenetic barrier for transcriptional activation. By considering brain cell type specific expression profiles that have been published only for non-demented individuals, we detail functional activities of selected neuron, microglia, and astrocyte-enriched genes (AGAP2, DUSP6 and GPR37L1, respectively), which are DNA hypermethylated at promoters in AD. We highlight future directions in MWAS including experimental confirmation, functional relevance to AD, cell type-specific temporal characterization, and mechanism investigation.
AB - Recent methylome-wide association studies (MWAS) in humans have solidified the concept that aberrant DNA methylation is associated with Alzheimer's disease (AD). We summarize these findings to improve the understanding of mechanisms governing DNA methylation pertinent to transcriptional regulation, with an emphasis of AD-associated promoter DNA hypermethylation, which establishes an epigenetic barrier for transcriptional activation. By considering brain cell type specific expression profiles that have been published only for non-demented individuals, we detail functional activities of selected neuron, microglia, and astrocyte-enriched genes (AGAP2, DUSP6 and GPR37L1, respectively), which are DNA hypermethylated at promoters in AD. We highlight future directions in MWAS including experimental confirmation, functional relevance to AD, cell type-specific temporal characterization, and mechanism investigation.
KW - Alzheimer's disease
KW - DNA methylation
KW - Promoter DNA hypermethylation
UR - http://www.scopus.com/inward/record.url?scp=85069932575&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2019.134403
DO - 10.1016/j.neulet.2019.134403
M3 - Review article
C2 - 31351091
AN - SCOPUS:85069932575
SN - 0304-3940
VL - 711
JO - Neuroscience Letters
JF - Neuroscience Letters
M1 - 134403
ER -