Requirements for utilization of CREB binding protein by hypersensitive site two of the beta-globin locus control region

Nucleic Acids Research
Kirby D JohnsonE H Bresnick

Abstract

Strong transactivation of the beta-globin genes is conferred by the beta-globin locus control region (LCR), which consists of four erythroid-specific DNase I hypersensitive sites (HS1-HS4). HS2 has a powerful enhancer activity dependent upon tandem binding sites for the erythroid cell- and megakaryocyte-specific transcription factor NF-E2. An important co-activator-mediating transactivation by HS2 is the histone acetyltransferase (HAT) CREB binding protein (CBP). We showed previously that recruitment of a GAL4-CBP fusion protein to HS2 largely bypassed the requirement of the NF-E2 sites for transactivation. To determine whether GAL4-CBP recruitment is sufficient for transactivation, we assessed the importance of cis-elements within HS2. Docking of GAL4-CBP upstream of an Agamma-globin promoter lacking HS2 only weakly activated the promoter, indicating that HS2 components are required for GAL4-CBP-mediated transactivation. Sequences upstream and downstream of the NF-E2 sites were required for maximal GAL4-CBP-mediated transactivation, and HAT catalytic activity of GAL4-CBP was critical. No single factor-binding site was required for GAL4-CBP-mediated transactivation. However, deletion of two sites, a CACC site and an E-box, abol...Continue Reading

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Citations

Sep 25, 2012·Nucleic Acids Research·Marloes L de GrooteMarianne G Rots
Feb 13, 2003·Current Opinion in Hematology·Kenneth R Peterson
Aug 6, 2013·Cell Reports·Farzin PourfarzadFrank Grosveld
Dec 19, 2002·The Journal of Biological Chemistry·Tamara NowlingAngie Rizzino
Aug 27, 2003·The Journal of Biological Chemistry·Chen ZhaoJun Ma

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