SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation.
Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced up-regulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation.
Ahlfors
Helena
H
Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Finland.
Limaye
Amita
A
Elo
Laura L
LL
Tuomela
Soile
S
Burute
Mithila
M
Gottimukkala
Kamal Vishnu P
KV
Notani
Dimple
D
Rasool
Omid
O
Galande
Sanjeev
S
Lahesmaa
Riitta
R
D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007231:Infant, Newborn; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D036961:Matrix Attachment Region Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D015415:Biomarkers; D050990:GATA3 Transcription Factor; C508599:IL5 protein, human; D015848:Interleukin-5; D036961:Matrix Attachment Region Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C076189:SATB1 protein, human; D008156:Luciferases