Transcriptional activation of human adult α-globin genes by hypersensitive site-40 enhancer: Function of nuclear factor-binding motifs occupied in erythroid cells

Irene Rombel, Kuang Yu Hu, Qingyi Zhang, Thalia Papayannopoulou, George Stamatoyannopoulos, Che Kun James Shen

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The developmental stage- and erythroid lineage-specific activation of the human embryonic ζ- and fetal/adult α-globin genes is controlled by an upstream regulatory element [hypersensitive site (HS)-40] with locus control region properties, a process mediated by multiple nuclear factor-DNA complexes. In vitro DNase I protection experiments of the two G+C-rich, adult α-globin promoters have revealed a number of binding sites for nuclear factors that are common to HeLa and K-562 extracts. However, genomic footprinting analysis has demonstrated that only a subset of these sites, clustered between -130 and +1, is occupied in an erythroid tissue-specific manner. The function of these in vivo-occupied motifs of the α-globin promoters, as well as those previously mapped in the HS-40 region, is assayed by site-directed mutagenesis and transient expression in embryonic/fetal erythroid K-562 cells. These studies, together with our expression data on the human embryonic ζ-globin promoter, provide a comprehensive view of the functional roles of individual nuclear factor-DNA complexes in the final stages of transcriptional activation of the human α-like globin promoters by the HS-40 element.

Original languageEnglish
Pages (from-to)6454-6458
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number14
DOIs
Publication statusPublished - Jul 3 1995
Externally publishedYes

Keywords

  • genomic footprinting
  • human α-globin promoter
  • site-directed mutagenesis
  • transient expression

ASJC Scopus subject areas

  • General

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