The Crucial Role of GATA-1 in CCR3 Gene Transcription: Modulated Balance by Multiple GATA Elements in the CCR3 Regulatory Region
- Authors
- Kim, Byung Soo; Uhm, Tae Gi; Lee, Seol Kyoung; Lee, Sin-Hwa; Kang, Jin Hyun; Park, Choon-Sik; Chung, Il Yup
- Issue Date
- Dec-2010
- Publisher
- American Association of Immunologists
- Citation
- Journal of Immunology, v.185, no.11, pp.6866 - 6875
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Immunology
- Volume
- 185
- Number
- 11
- Start Page
- 6866
- End Page
- 6875
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/39297
- DOI
- 10.4049/jimmunol.1001037
- ISSN
- 0022-1767
- Abstract
- GATA-1, a zinc finger-containing transcription factor, regulates not only the differentiation of eosinophils but also the expression of many eosinophil-specific genes. In the current study, we dissected CCR3 gene expression at the molecular level using several cell types that express varying levels of GATA-1 and CCR3. Chromatin immunoprecipitation analysis revealed that GATA-1 preferentially bound to sequences in both exon 1 and its proximal intron 1. A reporter plasmid assay showed that constructs harboring exon 1 and/or intron 1 sequences retained transactivation activity, which was essentially proportional to cellular levels of endogenous GATA-1. Introduction of a dominant-negative GATA-1 or small interfering RNA of GATA-1 resulted in a decrease in transcription activity of the CCR3 reporter. Both point mutation and EMSA analyses demonstrated that although GATA-1 bound to virtually all seven putative GATA elements present in exon 1-intron 1, the first GATA site in exon 1 exhibited the highest binding affinity for GATA-1 and was solely responsible for GATA-1-mediated transactivation. The fourth and fifth GATA sites in exon 1, which were postulated previously to be a canonical double-GATA site for GATA-1-mediated transcription of eosinophil-specific genes, appeared to play an inhibitory role in transactivation, albeit with a high affinity for GATA-1. Furthermore, mutation of the seventh GATA site ( present in intron 1) increased transcription, suggesting an inhibitory role. These data suggest that GATA-1 controls CCR3 transcription by interacting dynamically with the multiple GATA sites in the regulatory region of the CCR3 gene. The Journal of Immunology, 2010, 185: 6866-6875.
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