Positive transcriptional regulation of the human gamma-globin gene. Gamma PE is a novel nuclear factor with multiple binding sites near the gene

• Published in: The Journal of biological chemistry 1994-07, Vol.269 (30), p.19385-19393
• Main Authors: LLOYD, J. A, CASE, S. S, PONCE, E, LINGREL, J. B
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cross-Linking Reagents; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - radiation effects; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Globins - genetics; Humans; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Protein Binding; Regulatory Sequences, Nucleic Acid - genetics; Tissue Distribution; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Tumor Cells, Cultured; Ultraviolet Rays
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)32180-4

A novel nuclear factor involved in human gamma-globin gene regulation has been identified. Co-migrating and cross-competing complexes were formed with five individual fragments from the 5'- and 3'-flanking regions of the gene in DNA-protein binding assays. This indicates that a nuclear factor, termed gamma PE, has multiple binding sites near the gamma-globin gene. This characteristic is shared by other important factors in globin gene regulation, such as GATA-1. The five gamma PE binding sites can be placed in two categories based on DNA-protein binding affinity and DNA sequence composition. The consensus sequence for the two higher affinity binding sites is ATTANNNGGAANNCT(N)TNNNTAATGG and for the three lower affinity sites is AAAAN(A/T)A(A/T)TT. Both the ATTA and the TAAT motifs of a high affinity binding site are required for efficient DNA-protein binding. The tissue distribution of gamma PE binding activity is broad, including both erythroid and non-erythroid cell types. Transcription of either a gamma-globin or heterologous promoter is increased in the presence of nearby gamma PE binding sites. Therefore, gamma PE may be involved in activating the gamma-globin gene in fetal erythroid cells. UV cross-linking analysis indicates that the major protein interacting with a high affinity gamma PE binding site has a molecular mass of 108 kDa.