MafK/NF-E2 p18 is required for β-globin genes activation by mediating the proximity of LCR and active β-globin genes in MEL cell line
- 作者：Mei-Jun Du ; Xiang Lv ; De-Long Hao ; Guo-Wei Zhao ; Xue-Song Wu ; Feng Wu ; De-Pei Liu ; Chih-Chuan Liang
- 关键词：β ; -Globin gene ; MafK ; NF-E2 ; Looping ; 3C
- 刊名：The International Journal of Biochemistry and Cell Biology
- 出版年：2008
- 期刊代码：127_13572725
- 类别：med
- 出版时间：2008
- 卷：40
- 期：8
- 页码：1481-1493
- 文件大小：978 K
摘要
Evidences indicate that locus control region (LCR) of β-globin spatially closes to the downstream active gene promoter to mediate the transcriptional activation by looping. DNA binding proteins may play an important role in the looping formation. NF-E2 is one of the key transcription factors in β-globin gene transcriptional activation. To shed light on whether NF-E2 is involved in this process, DS19MafKsiRNA cell pools were established by specifically knocked down the expression of MafK/NF-E2 p18, one subunit of NF-E2 heterodimer. In the above cell pools, it was observed that the occupancy efficiency of NF-E2 on β-globin gene locus and the expression level of β-globin genes were decreased. H3 acetylation, H3-K4 methylation and the deposition of RNA polymerase II, but not the recruitment of GATA-1, were also found reduced at the β-globin gene cluster. Chromosome Conformation Capture (3C) assay showed that the cross-linking frequency between the main NF-E2 binding site HS2 and downstream structural genes was reduced compared to the normal cell. This result demonstrated that MafK/NF-E2 p18 recruitment was involved in the physical proximity of LCR and active β-globin genes upon β-globin gene transcriptional activation.