The long terminal repeat (LTR) of ERV-9 human endogenous retrovirus binds to NF-Y in the assembly of an active LTR enhancer complex NF-Y/MZF1/GATA-2

Xiuping Yu, Xingguo Zhu, Wenhu Pi, Jianhua Ling, Lan Ko, Yoshihiko Takeda, Dorothy Tuan Lo

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The solitary ERV-9 long terminal repeat (LTR) located upstream of the HS5 site in the human β-globin locus control region exhibits prominent enhancer activity in embryonic and erythroid cells. The LTR enhancer contains 14 tandemly repeated subunits with recurrent CCAAT, GTGGGGA, and GATA motifs. Here we showed that in erythroid K562 cells these DNA motifs bound the following three transcription factors: ubiquitous NF-Y and hematopoietic MZF1 and GATA-2. These factors and their target DNA motifs exhibited a hierarchy of DNA/protein and protein/protein binding affinities: NF-Y/CCAAT > NF-Y/GATA-2 > NF-Y/MZF1 > MZF1/GT-GGGGA; GATA-2/GATA. Through protein/protein interactions, NF-Y bound at the CCAAT motif recruited MZF1 and GATA-2, but not Sp1 and GATA-1, and stabilized their binding to the neighboring GTGGGGA and GATA sites to assemble a novel LTR enhancer complex, NF-Y/MZF1/GATA-2. In the LTR-HS5-ep-GFP plasmid integrated into K562 cells, mutation of the CCAAT motif in the LTR enhancer to abolish NF-Y binding inactivated the enhancer, closed down the chromatin structure of the ε-globin promoter, and silenced transcription of the green fluorescent protein gene. The results indicated that NF-Y bound at the CCAAT motifs assembled a robust LTR enhancer complex, which could act over the intervening DNA to remodel the chromatin structure and to stimulate the transcription of the downstream gene locus.

Original languageEnglish (US)
Pages (from-to)35184-35194
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number42
DOIs
StatePublished - Oct 21 2005

Fingerprint

Endogenous Retroviruses
Terminal Repeat Sequences
Erythroid Cells
Nucleotide Motifs
Globins
K562 Cells
DNA
Transcription
Chromatin
CCAAT-Binding Factor
Proteins
Genes
Locus Control Region
Green Fluorescent Proteins
Protein Binding
Plasmids
Transcription Factors
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The long terminal repeat (LTR) of ERV-9 human endogenous retrovirus binds to NF-Y in the assembly of an active LTR enhancer complex NF-Y/MZF1/GATA-2. / Yu, Xiuping; Zhu, Xingguo; Pi, Wenhu; Ling, Jianhua; Ko, Lan; Takeda, Yoshihiko; Tuan Lo, Dorothy.

In: Journal of Biological Chemistry, Vol. 280, No. 42, 21.10.2005, p. 35184-35194.

Research output: Contribution to journalArticle

Yu, Xiuping ; Zhu, Xingguo ; Pi, Wenhu ; Ling, Jianhua ; Ko, Lan ; Takeda, Yoshihiko ; Tuan Lo, Dorothy. / The long terminal repeat (LTR) of ERV-9 human endogenous retrovirus binds to NF-Y in the assembly of an active LTR enhancer complex NF-Y/MZF1/GATA-2. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 42. pp. 35184-35194.
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AU - Ko, Lan

AU - Takeda, Yoshihiko

AU - Tuan Lo, Dorothy

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