Open AccessMitogen-activated protein kinases enhance long-range activation by the β-globin locus control region
Author(s) -
Wayne K. Versaw,
Volker Blank,
Nancy C. Andrews,
Emery H. Bresnick
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.15.8756
Subject(s) - locus control region , enhancer , microbiology and biotechnology , biology , transactivation , hypersensitive site , transcription factor , activator (genetics) , dnase i hypersensitive site , kinase , promoter , globin , gene , gene expression , genetics
The human β-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 β-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.