title: Different GATA factors dictate CCR3 transcription in allergic inflammatory cells in a cell type-specific manner.
abstract: The chemokine receptor CCR3 is expressed in prominent allergic inflammatory cells, including eosinophils, mast cells, and Th2 cells. We previously identified a functional GATA element within exon 1 of the CCR3 gene that is responsible for GATA-1-mediated CCR3 transcription. Because allergic inflammatory cells exhibit distinct expression patterns of different GATA factors, we investigated whether different GATA factors dictate CCR3 transcription in a cell type-specific manner. GATA-2 was expressed in EoL-1 eosinophilic cells, GATA-1 and GATA-2 were expressed in HMC-1 mast cells, and GATA-3 was preferentially expressed in Jurkat cells. Unlike a wild-type CCR3 reporter, reporters lacking the functional GATA element were not active in any of the three cell types, implying the involvement of different GATA factors in CCR3 transcription. RNA interference assays showed that small interfering RNAs specific for different GATA factors reduced CCR3 reporter activity in a cell type-specific fashion. Consistent with these findings, chromatin immunoprecipitation and EMSA analyses demonstrated cell type-specific binding of GATA factors to the functional GATA site. More importantly, specific inhibition of the CCR3 reporter activity by different GATA small interfering RNAs was well preserved in respective cell types differentiated from cord blood; in particular, GATA-3 was entirely responsible for reporter activity in Th2 cells and replaced the role predominantly played by GATA-1 and GATA-2. These results highlight a mechanistic role of GATA factors in which cell type-specific expression is the primary determinant of transcription of the CCR3 gene in major allergic inflammatory cells.
authors: Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University, Gyeonggi-do 426-791, Republic of Korea.
authors: Su-Kang
authors: SK
authors: Kong
authors: Byung Soo
authors: BS
authors: Kim
authors: Tae Gi
authors: TG
authors: Uhm
authors: Wonyong
authors: W
authors: Lee
authors: Gap Ryol
authors: GR
authors: Lee
authors: Choon-Sik
authors: CS
authors: Park
authors: Chul-Hoon
authors: CH
authors: Lee
authors: Il Yup
authors: IY
authors: Chung
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D023061:Gene Order; D020868:Gene Silencing; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D054397:Receptors, CCR3 / Q000235:genetics*; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D050980:GATA Transcription Factors; D054397:Receptors, CCR3