Developmental regulation of the human β‐globin cluster

STEPHEN M. Jane, PERSIS Amrolia, JOHN M. Cunningham

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Abstract

Expression of the genes of the human β‐globin cluster is subject to stringent developmental regulation. An integral component of this control is competition between the γ‐ and β‐promoters for the upstream regulatory sequences of the Locus Control Region (LCR). We have defined two stage selector elements (SSE and SSE‐2), located in the proximal γ‐promoter and y‐gene 5′UTR which mediate the preferential interaction of the γ‐gene with the L CR in the foetal developmental stage. The activity of both elements is dependent upon the binding of foetal and erythroid‐specific proteins. We have purified the protein binding the proximal SSE and characterised it as a complex between the ubiquitous transcription factor CP2 and a 40 kD partner protein. Comparative studies between human CP2 and the chicken stage selector protein, NF‐E4, demonstrate homology between the protein complexes. These findings demonstrate that competitive silencing of globin genes mediated by developmentally‐specific protein complexes is conserved in evolution.

Original languageEnglish
Pages (from-to)865-869
Number of pages5
JournalAustralian and New Zealand Journal of Medicine
Volume25
Issue number6
DOIs
Publication statusPublished - 1 Jan 1995
Externally publishedYes

Keywords

  • gene regulation.
  • Globin
  • transcription

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