PMID- 38351418
OWN - NLM
STAT- Publisher
LR  - 20240214
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
DP  - 2024 Feb 14
TI  - H3K4 Trimethylation Mediate Hyperhomocysteinemia Induced Neurodegeneration via 
      Suppressing Histone Acetylation by ANP32A.
LID - 10.1007/s12035-024-03995-y [doi]
AB  - Homocysteine (Hcy) is an independent and serious risk factor for dementia, 
      including Alzheimer's disease (AD), but the precise mechanisms are still poorly 
      understood. In the current study, we observed that the permissive histone mark 
      trimethyl histone H3 lysine 4 (H3K4me3) and its methyltransferase KMT2B were 
      significantly elevated in hyperhomocysteinemia (HHcy) rats, with impairment of 
      synaptic plasticity and cognitive function. Further research found that histone 
      methylation inhibited synapse-associated protein expression, by suppressing 
      histone acetylation. Inhibiting H3K4me3 by downregulating KMT2B could effectively 
      restore Hcy-inhibited H3K14ace in N2a cells. Moreover, chromatin 
      immunoprecipitation revealed that Hcy-induced H3K4me3 resulted in ANP32A mRNA and 
      protein overexpression in the hippocampus, which was regulated by increased 
      transcription Factor c-fos and inhibited histone acetylation and 
      synapse-associated protein expression, and downregulating ANP32A could reverse 
      these changes in Hcy-treated N2a cells. Additionally, the knockdown of KMT2B 
      restored histone acetylation and synapse-associated proteins in Hcy-treated 
      primary hippocampal neurons. These data have revealed a novel crosstalk mechanism 
      between KMT2B-H3K4me3-ANP32A-H3K14ace, shedding light on its role in Hcy-related 
      neurogenerative disorders.
CI  - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Chai, Gao-Shang
AU  - Chai GS
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China. chaigaoshang@jiangnan.edu.cn.
FAU - Gong, Juan
AU  - Gong J
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China.
FAU - Mao, Yu-Ming
AU  - Mao YM
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China.
FAU - Wu, Jia-Jun
AU  - Wu JJ
AD  - Department of Electrophysiology, Wuhan Children's Hospital (Wuhan Maternal and 
      Children's Healthcare Center), Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan, Hubei, 430010, People's Republic of China.
FAU - Bi, Shu-Guang
AU  - Bi SG
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China.
FAU - Wang, Fangzhou
AU  - Wang F
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China.
FAU - Zhang, Yu-Qi
AU  - Zhang YQ
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China.
FAU - Shen, Meng-Ting
AU  - Shen MT
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China.
FAU - Lei, Zhuo-Ya
AU  - Lei ZY
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China.
FAU - Nie, Yun-Juan
AU  - Nie YJ
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China.
FAU - Yu, Haitao
AU  - Yu H
AD  - Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, 
      Wuxi, Jiangsu, 214122, People's Republic of China. yu_haitao@jiangnan.edu.cn.
LA  - eng
GR  - 81601121/the National Natural Science Foundation of China/
GR  - BK20211238/Natural Science Foundation of Jiangsu Province/
GR  - 2020M681491/China Postdoctoral Science Foundation/
GR  - 2020Z037/Jiangsu Province Postdoctoral Science Foundation/
GR  - SZCY-003/Six Talent Peaks Project in Jiangsu Province/
GR  - JUSRP123070/Fundamental Research Funds for the Central Universities/
PT  - Journal Article
DEP - 20240214
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
SB  - IM
OTO - NOTNLM
OT  - ANP32A
OT  - Alzheimer' disease
OT  - Histone acetylation
OT  - Histone methylation
OT  - Homocysteine
OT  - Neurodegeneration
EDAT- 2024/02/14 06:43
MHDA- 2024/02/14 06:43
CRDT- 2024/02/14 00:02
PHST- 2023/12/05 00:00 [received]
PHST- 2024/01/29 00:00 [accepted]
PHST- 2024/02/14 06:43 [medline]
PHST- 2024/02/14 06:43 [pubmed]
PHST- 2024/02/14 00:02 [entrez]
AID - 10.1007/s12035-024-03995-y [pii]
AID - 10.1007/s12035-024-03995-y [doi]
PST - aheadofprint
SO  - Mol Neurobiol. 2024 Feb 14. doi: 10.1007/s12035-024-03995-y.