Mitogen-activated protein kinases enhance long-range activation by the beta-globin locus control region.

Published

Journal Article

The human beta-globin locus control region (LCR), which consists of four erythroid-specific DNase I hypersensitive sites (HS1-HS4), functions over a long distance to control the transcription, chromatin structure, and replication of the beta-globin genes. We have used stable transfection assays to show that activation of the mitogen-activated protein (MAP) kinase pathway by low concentrations of the phorbol ester phorbol 12-tetradecanoate 13-acetate (TPA) induces enhancer activity of the LCR subregion HS2, but not HS3. Although HS2 enhancer activity is diminished with increasing distance from the promoter, the relative level of induction by TPA is independent of HS2-promoter distance. Mutation of cis-elements within HS2 reveals that the tandem-binding sites for the hematopoietic-specific transcription factor NF-E2 are required for induction by TPA, and induction is conferred by expressing NF-E2 in an NF-E2-null cell line. These results show that MAP kinases target factors functioning through the NF-E2 sites to enhance long-range transactivation by the LCR.

Full Text

Duke Authors

Cited Authors

  • Versaw, WK; Blank, V; Andrews, NM; Bresnick, EH

Published Date

  • July 21, 1998

Published In

Volume / Issue

  • 95 / 15

Start / End Page

  • 8756 - 8760

PubMed ID

  • 9671751

Pubmed Central ID

  • 9671751

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.95.15.8756

Language

  • eng

Conference Location

  • United States