Research

The figure shows a simplified scheme of the erythropoietin (Epo)-gene and some of the most important transcription factors required for transcription in hypoxia. One particularity of the Epo-gene is the fact that the hypoxia-responsive element (HRE) is located in the 3’-region of the gene (downstream in respect to the polyA-signal). This HRE is recognized and bound by the heterodimeric transcription factors HIF-1α/1β and/or HIF-2α/1β. A Third HIF-α subunit is described in the literature but the function of this subunit is still uncertain. HIF-binding to the HRE alone is not sufficient for an efficient transcription under hypoxia, other transcription factors have to bind sequences in close proximity to the HRE (f. i. HNF-4 has to bind to the DR-2 element 8 base pairs downstream of the HRE). Transcription factor-binding does not initiate transcription per se, other transcriptional co-activators like P300 and accessory proteins like SRC-1 have to form an initiation-complex, guiding RNA-polymerase 2 to the start point of transcription within the Epo-promoter. The Epo-promoter does not contain a TATA-box, instead a GATA-sequence is found at position -35. In normoxia, this GATA-sequence is occupied by one member of the GATA-transcription factor family. GATA-2 was found to act as a repressor under normoxia and dissociates from the promoter upon the onset of hypoxia.