NFκB- and AP-1-mediated DNA looping regulates matrix metalloproteinase-9 transcription in TNF-α-treated human leukemia U937 cells

被引:32
作者
Chen, Ying-Jung [1 ]
Chang, Long-Sen [1 ,2 ]
机构
[1] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 804, Taiwan
[2] Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung 807, Taiwan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS | 2015年 / 1849卷 / 10期
关键词
MMP-9; DNA looping; TNF-alpha; NF kappa B/p65; AP-1/c-Jun; Histone acetylation; NECROSIS-FACTOR-ALPHA; INDUCED MMP-9 EXPRESSION; CREB-BINDING PROTEIN; SMOOTH-MUSCLE-CELLS; MYELOID-LEUKEMIA; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; C-JUN; MYELOGENOUS LEUKEMIA; CANCER PROGRESSION;
D O I
10.1016/j.bbagrm.2015.07.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aim of this study is to explore the spatial association of critical genomic elements in the effect of TNF-alpha on matrix metalloproteinase-9 (MMP-9) expression in human leukemia U937 cells. TNF-alpha, up-regulated MMP-9 protein expression and mRNA level in U937 cells, and Akt-mediated-NF kappa B/p65 activation and JNK-mediated c-Jun activation were proven to be involved in TNF-alpha-induced MMP-9 up-regulation. Promoter luciferase activity assay revealed that NF kappa B (nt-600) and AP-1 (nt-79) binding sites were crucial for TNF-alpha-induced transcription of MMP-9 gene. The results of a chromatin immunoprecipitation assay indicated that TNF-alpha reduced histone deacetylase-1 (HDAC-1) recruitment but increased p300 (a histone acetyltransferase) recruitment to MMP-9 promoter regions surrounding NF kappa B and AP-1 binding sites. Consistently, TNF-alpha increased enrichment of the acetylated histone H3 mark on MMP-9 promoter regions. DNA affinity purification assay revealed that p300 and HDAC1 could bind oligonucleotides containing AP-1/c-Jun and NF kappa B/p65 binding sites. Chromosome conformation capture assay showed that TNF-alpha stimulated chromosomal loops in the MMP-9 promoter via NF kappa B/p65 and AP-1/c-Jun. The p300-associated acetyltransferase activity was crucial for p65/c-Jun-mediated DNA looping, and inhibition of HDAC activity increased the level of DNA looping. Reduction in the level of DNA looping eliminated all TNF-alpha-stimulated MMP-9 up-regulation. Taken together, our data suggest that p65/c-Jun-mediated DNA looping is involved in TNF-alpha-induced MMP-9 up-regulation and that the recruitment of p300 or HDAC1 to NF kappa B and AP-1 binding sites modifies the level of DNA looping. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:1248 / 1259
页数:12
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