Role of e boxes in the β-globin locus control region

L. Hlnilski, W. Miller, R. C. Hardison

Research output: Contribution to journalArticlepeer-review

Abstract

Regulated expression of the β-globin gene cluster requires the combined action oi the proximal e, y, 6, and β-globin gene promoters and the distal Locus Control Region (I.CR). The I.CR contains 5 DNAse 1 hypersensitive sites (IIS1 -5) located 6-22 kh upstream of the t:-globin gene. A sub-fragment of'HS2 capable of conferring the properties of domain opening and enhancement contains API/NFE-2. CACCC, and GATA-1 binding sites, as well as conserved sequence blocks that \vc identified through phylogenetic footprinting. Two of these blocks are K box hexamers (CAGATCi) that bind basic helix-loop-helix (bHLH) proleins. We find that the E boxes contribute to the enhancement of globin gene expression by HS2. Furthermore, we show that TAL1/SCL. a bHLH protein required for all hematopoietic lineages; USF; and other proteins bind specifically to these sites. Currently, we are studying the effect of post-translalional modification on the function ot these K box binding proteins.

Original languageEnglish (US)
Pages (from-to)A933
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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