The association and significance of H3K27me3 and a folate metabolic gene ACat2 in neural tube defects.
To study the association between the expression of H3K27me3 and ACat2 (a folate metabolic protein), in order to elucidate the protective mechanism of folic acid (FA) in neural tube defects (NTDs).



Eighteen female SD rats were randomly divided into normal, NTD and FA group. NTD group was induced by all-trans retinoic acid (ATRA) at E10d. FA group was fed with FA supplementation since 2 weeks before pregnancy, followed by ATRA induction. At E15d, FA level in the embryonic neural tube was determined by ELISA. Neural stem cells (NSCs) were isolated. Cell proliferation was compared by CCK-8 assay. The differentiation potency was assessed by immunocytochemical staining. H3K27me3 expression was measured by immunofluorescence method and Western blot. ACat2 mRNA expression was detected by qRT-PCR.



Cultured NSCs formed numerous Nestin-positive neurospheres. After 5 days, they differentiated into NSE-positive neurons and GFAP-positive astrocytes. When compared with controls, the FA level in NTD group was significantly lower, the ability of cell proliferation and differentiation was significantly reduced, H3K27me3 expression was increased, and ACat2 mRNA expression was decreased (P <0.05). The intervention of FA notably reversed these changes (P <0.05). H3K27me3 expression was negatively correlated with the FA level (rs = -0.908, P <0.01) and ACat2 level (rs = -0.879, P <0.01) in the neural tube.



The increased H3K27me3 expression might cause a disorder of folate metabolic pathway by silencing ACat2 expression, leading to reduced proliferation and differentiation of NSCs, and ultimately the occurrence of NTD. FA supplementation may reverse this process.
Graduate School, Ningxia Medical University, Ningxia, China.
Sifan
S
Zhai
Department of General Surgery, Suqian People's Hospital, Suqian, Jiangsu, China.
Mingzuo
M
Zhao
Tai'an Hospital of Traditional Chinese Medicine, Tai'an, Shandong, China.
Changcheng
C
Zhou
No. 215 Hospital, Sino Shanxi Nuclear Industry Group, Xi'an, Shangxi, China.
Fenggang
F
Lu
Graduate School, Ningxia Medical University, Ningxia, China.
Huankai
H
Zhang
Department of General Surgery, General Hospital of Ningxia Medical University, Ningxia, China.
Li
L
Na
Department of General Surgery, General Hospital of Ningxia Medical University, Ningxia, China.
Shanshan
S
Feng
Department of General Surgery, General Hospital of Ningxia Medical University, Ningxia, China.
Xiaoxin
X
Qiang
Department of Scientific Research, General Hospital of Ningxia Medical University, 804 South Victory Street, Yinchuan, Ningxia, China. jiayonglushaoqi@sohu.com.
Yong
Y
Du
D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009436:Neural Tube Defects / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin
D006657:Histones; D014212:Tretinoin; D005492:Folic Acid; D000101:Acetyl-CoA C-Acetyltransferase
Epigenetics; Folic acid; H3K27me3; Neural stem cells; Neural tube defects