Figure 7.

Model of SPI1-mediated gene repression in murine erythroleukaemia. Working hypothesis representing one of the mechanisms of gene repression by SPI1 based on the data described in this manuscript. During normal erythroid differentiation, GATA1 binds active enhancers and induces erythroid gene expression; SPI1 is barely expressed in CFU-E. When SPI1 is highly expressed, it binds to SPI1 binding sites at enhancers and, by interacting with HDAC1, triggers HDAC1-mediated deacetylation of enhancers and associated gene promoters. Consequently, chromatin is slightly condensed at enhancers and closed down around the TSS, the total RNA pol II (RNP2) quantity is reduced at the TSS and, the RNA transcription is decreased. Reduction of transcribed RNA molecules is associated with the venue of PRC2 to the chromatin and PRC2-mediated H3K27 methylation activity is potentially emphasized by SPI1. Thereby, the PRC2 complex reinforces HDAC1 transcriptional inhibition.