PMID- 31737059
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 10
DP  - 2019
TI  - Regulatory Factor X1 Downregulation Contributes to Monocyte Chemoattractant 
      Protein-1 Overexpression in CD14+ Monocytes via Epigenetic Mechanisms in Coronary 
      Heart Disease.
PG  - 1098
LID - 10.3389/fgene.2019.01098 [doi]
LID - 1098
AB  - Monocyte chemoattractant protein 1 (MCP1) affects the chemotaxis of monocytes and 
      is a key chemokine closely related to the development of atherosclerosis (AS). 
      Compared with healthy controls, coronary heart disease (CAD) patients show 
      significantly upregulated plasma concentrations and mRNA expression of MCP1 in 
      CD14+ monocytes. However, the specific regulatory mechanism of MCP1 
      overexpression in AS is still unclear. Our previous research indicated that there 
      was no significant difference in the H3K4 and H3K27 tri-methylation of the MCP1 
      promoter in CD14+ monocytes from CAD versus non-CAD patients, but the H3 and H4 
      acetylation of the MCP1 promoter was increased in CD14+ monocytes from CAD 
      patients. We further found that the H3K9 tri-methylation of the MCP1 promoter in 
      CD14+ monocytes from CAD patients was decreased, but the DNA methylation levels 
      did not differ markedly from those in non-CAD patients. Our previous work showed 
      that the level of regulatory factor X1 (RFX1) was markedly reduced in CD14+ 
      monocytes from CAD patients and played an important role in the progression of AS 
      by regulating epigenetic modification. In this study, we investigated whether 
      RFX1 and epigenetic modifications mediated by RFX1 contribute to the 
      overexpression of MCP1 in activated monocytes in CAD patients. We found that the 
      enrichment of RFX1, histone deacetylase 1 (HDAC1), and suppressor of variegation 
      3-9 homolog 1 (SUV39H1) in the MCP1 gene promoter region were decreased in CD14+ 
      monocytes from CAD patients and in healthy CD14+ monocytes treated with 
      low-density lipoprotein (LDL). Chromatin immunoprecipitation (ChIP) assays 
      identified MCP1 as a target gene of RFX1. Overexpression of RFX1 increased the 
      recruitments of HDAC1 and SUV39H1 and inhibited the expression of MCP1 in CD14+ 
      monocytes. In contrast, knockdown of RFX1 in CD14+ monocytes reduced the 
      recruitments of HDAC1 and SUV39H1 in the MCP1 promoter region, thereby 
      facilitating H3 and H4 acetylation and H3K9 tri-methylation in this region. In 
      conclusion, our results indicated that RFX1 expression deficiency in CD14+ 
      monocytes from CAD patients contributed to MCP1 overexpression via a deficiency 
      of recruitments of HDAC1 and SUV39H1 in the MCP1 promoter, which highlighted the 
      vital role of RFX1 in the pathogenesis of CAD.
CI  - Copyright (c) 2019 Jia, Yang, Du, Gao, Cao, Yao, Guo and Zhao.
FAU - Jia, Sujie
AU  - Jia S
AD  - Department of Pharmacy, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
FAU - Yang, Shuang
AU  - Yang S
AD  - Department of Pharmacy, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Du, Pei
AU  - Du P
AD  - Department of Pharmacy, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Gao, Keqin
AU  - Gao K
AD  - Department of Pharmacy, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Department of Pharmacy, Weifang People's Hospital, Weifang, China.
FAU - Cao, Yu
AU  - Cao Y
AD  - Dapartment of Cardiology, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Yao, Baige
AU  - Yao B
AD  - Department of Pharmacy, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Guo, Ren
AU  - Guo R
AD  - Department of Pharmacy, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Zhao, Ming
AU  - Zhao M
AD  - Dapartment of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The 
      Second Xiangya Hospital, Central South University, Changsha, China.
LA  - eng
PT  - Journal Article
DEP - 20191101
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC6838212
OTO - NOTNLM
OT  - epigenetics
OT  - histone acetylation
OT  - monocyte chemoattractant protein-1
OT  - monocytes
OT  - regulatory factor X1
EDAT- 2019/11/19 06:00
MHDA- 2019/11/19 06:01
PMCR- 2019/11/01
CRDT- 2019/11/19 06:00
PHST- 2019/06/28 00:00 [received]
PHST- 2019/10/11 00:00 [accepted]
PHST- 2019/11/19 06:00 [entrez]
PHST- 2019/11/19 06:00 [pubmed]
PHST- 2019/11/19 06:01 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - 10.3389/fgene.2019.01098 [doi]
PST - epublish
SO  - Front Genet. 2019 Nov 1;10:1098. doi: 10.3389/fgene.2019.01098. eCollection 2019.