title: Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3.
abstract: Differentiation of naive CD4 T cells into Th2 cells is accompanied by chromatin remodeling and increased expression of a set of Th2-specific genes, including those encoding Th2 cytokines. IL-4-mediated STAT6 activation induces high levels of transcription of GATA3, a master regulator of Th2 cell differentiation, and enforced expression of GATA3 induces Th2 cytokine expression. However, it remains unclear whether the expression of other Th2-specific genes is induced directly by GATA3. A genome-wide unbiased chromatin immunoprecipitation assay coupled with massive parallel sequencing analysis revealed that GATA3 bound to 1279 genes selectively in Th2 cells, and 101 genes in both Th1 and Th2 cells. Simultaneously, we identified 26 highly Th2-specific STAT6-dependent inducible genes by DNA microarray analysis-based three-step selection processes, and among them 17 genes showed GATA3 binding. We assessed dependency on GATA3 for the transcription of these 26 Th2-specific genes, and 10 genes showed increased transcription in a GATA3-dependent manner, whereas 16 genes showed no significant responses. The transcription of the 16 GATA3-nonresponding genes was clearly increased by the introduction of an active form of STAT6, STAT6VT. Therefore, although GATA3 has been recognized as a master regulator of Th2 cell differentiation, many Th2-specific genes are not regulated by GATA3 itself, but in collaboration with STAT6.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Horiuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Onodera
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse