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Background  MTG16, MTGR1 and ETO are nuclear transcriptional corepressors of the human ETO protein family. MTG16 is implicated in hematopoietic development and in controlling erythropoiesis/megakaryopoiesis. Furthermore, ETO homologue genes are 3'participants in leukemia fusions generated by chromosomal translocations responsible of hematopoietic dysregulation. We tried to identify structural and functional promoter elements of  MTG16  and  MTGR1  genes in order to find associations between their regulation and hematopoiesis.    Results  5' deletion examinations and luciferase reporter gene studies indicated that a 492 bp sequence upstream of the transcription start site is essential for transcriptional activity by the  MTG16  promoter. The TATA- and CCAAT-less promoter with a GC box close to the start site showed strong reporter activity when examined in erythroid/megakaryocytic cells. Mutation of an evolutionary conserved GATA -301 consensus binding site repressed promoter function. Furthermore, results from  in vitro  antibody-enhanced electrophoretic mobility shift assay and  in vivo  chromatin immunoprecipitation indicated binding of GATA-1 to the GATA -301 site. A role of GATA-1 was also supported by transfection of small interfering RNA, which diminished  MTG16  expression. Furthermore, expression of the transcription factor HERP2, which represses GATA-1, produced strong inhibition of the  MTG16  promoter reporter consistent with a role of GATA-1 in transcriptional activation. The TATA-less and CCAAT-less  MTGR1  promoter retained most of the transcriptional activity within a -308 to -207 bp region with a GC-box-rich sequence containing multiple SP1 binding sites reminiscent of a housekeeping gene with constitutive expression. However, mutations of individual SP1 binding sites did not repress promoter function; multiple active SP1 binding sites may be required to safeguard constitutive  MTGR1  transcriptional activity. The observed repression of  MTG16 / MTGR1  promoters by the leukemia associated  AML1 - ETO  fusion gene may have a role in hematopoietic dysfunction of leukemia.    Conclusions  An evolutionary conserved GATA binding site is critical in transcriptional regulation of the  MTG16  promoter. In contrast, the  MTGR1  gene depends on a GC-box-rich sequence for transcriptional regulation and possible ubiquitous expression. Our results demonstrate that the  ETO  homologue promoters are regulated differently consistent with hematopoietic cell-type- specific expression and function.

The leukemia associated nuclear corepressor ETO homologue genes MTG16 and MTGR1 are regulated differently in hematopoietic cells