NF-Y Recruits Both Transcription Activator and Repressor to Modulate Tissue- and Developmental Stage-Specific Expression of Human γ-Globin Gene

Xingguo Zhu, Yongchao Wang, Wenhu Pi, Hui Liu, Amittha Wickrema, Dorothy Tuan Lo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The human embryonic, fetal and adult β-like globin genes provide a paradigm for tissue- and developmental stage-specific gene regulation. The fetal γ-globin gene is expressed in fetal erythroid cells but is repressed in adult erythroid cells. The molecular mechanism underlying this transcriptional switch during erythroid development is not completely understood. Here, we used a combination of in vitro and in vivo assays to dissect the molecular assemblies of the active and the repressed proximal γ-globin promoter complexes in K562 human erythroleukemia cell line and primary human fetal and adult erythroid cells. We found that the proximal γ-globin promoter complex is assembled by a developmentally regulated, general transcription activator NF-Y bound strongly at the tandem CCAAT motifs near the TATA box. NF-Y recruits to neighboring DNA motifs the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A, which in turn recruit erythroid repressor GATA-1 and general repressor COUP-TFII to form respectively the NF-Y/GATA-2 transcription activator hub and the BCL11A/COUP-TFII/GATA-1 transcription repressor hub. Both the activator and the repressor hubs are present in both the active and the repressed γ-globin promoter complexes in fetal and adult erythroid cells. Through changes in their levels and respective interactions with the co-activators and co-repressors during erythroid development, the activator and the repressor hubs modulate erythroid- and developmental stage-specific transcription of γ-globin gene.

Original languageEnglish (US)
Article numbere47175
JournalPloS one
Volume7
Issue number10
DOIs
StatePublished - Oct 10 2012

Fingerprint

Globins
Transcription
Erythroid Cells
transcription (genetics)
Genes
developmental stages
Tissue
promoter regions
genes
cells
TATA box
human cell lines
Co-Repressor Proteins
Leukemia, Erythroblastic, Acute
TATA Box
Nucleotide Motifs
Gene expression
tissues
Assays
Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

NF-Y Recruits Both Transcription Activator and Repressor to Modulate Tissue- and Developmental Stage-Specific Expression of Human γ-Globin Gene. / Zhu, Xingguo; Wang, Yongchao; Pi, Wenhu; Liu, Hui; Wickrema, Amittha; Tuan Lo, Dorothy.

In: PloS one, Vol. 7, No. 10, e47175, 10.10.2012.

Research output: Contribution to journalArticle

Zhu, Xingguo ; Wang, Yongchao ; Pi, Wenhu ; Liu, Hui ; Wickrema, Amittha ; Tuan Lo, Dorothy. / NF-Y Recruits Both Transcription Activator and Repressor to Modulate Tissue- and Developmental Stage-Specific Expression of Human γ-Globin Gene. In: PloS one. 2012 ; Vol. 7, No. 10.
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