Upstream stimulatory factor and TFII-I are ubiquitously expressed helix-loop-helix transcription factors that interact with E-box sequences and or initiator elements. We previously demonstrated that upstream stimulatory factor is an activator of β-globin gene expression whereas TFII-I is a repressor. In the present study, we demonstrate that upstream stimulatory factor interacts with the coactivator p300 and that this interaction is restricted to erythroid cells expressing the adult β-globin gene. Furthermore, we demonstrate that Suz12, a component of the polycomb repressor complex 2, is recruited to the β-globin gene. Reducing expression of Suz12 significantly activates β-globin gene expression in an erythroid cell line with an embryonic phenotype. Suz12 also interacts with the adult β-globin gene during early stages of erythroid differentiation of mouse embryonic stem cells. Our data suggest that TFII-I contributes to the recruitment of the polycomb repressor complex 2 complex to the β-globin gene. Together, these data demonstrate that the antagonistic activities of upstream stimulatory factor and TFII-I on β-globin gene expression are mediated at least in part by protein complexes that render the promoter associated chromatin accessible or inaccessible for the transcription complex.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology