SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation

: Ahlfors Helena, Limaye Amita, Elo Laura L, Tuomela Soile, Burute Mithila, Gottimukkala Kamal Vishnu P, Notani Dimple, Rasool Omid, Galande Sanjeev, Lahesmaa Riitta

Publisher: AMER SOC HEMATOLOGY

: 2010

: Blood

: BLOOD

: 9

: 116

: 9

: 1443

: 1453

: 11

: 0006-4971

DOI: https://doi.org/10.1182/blood-2009-11-252205

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 upregulation 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. (Blood. 2010;116(9):1443-1453)

Ahlfors_Blood_2010.pdf