Die epigenetische Lokalisation der aktivierenden Histonmodifikationen während der Erythropoese ist abhängig von der ABO-Blutgruppe und erklärt die Unterschiede im erythroiden Potenzial von Trägern der Blutgruppe B im Vergleich zu A und O
Romy Kronstein-Wiedemann (Dresden / DE), Madeleine Teichert (Dresden / DE), Michael Seifert (Dresden / DE), Stephan Künzel (Dresden / DE), Kristina Hölig (Dresden / DE), Torsten Tonn (Dresden / DE; Frankfurt a. M. / DE)
The ABO blood group (BG) system is the most important factor in clinical transfusion and transplantation medicine and its antigens are involved in the development of various human diseases. Previously, we demonstrated that the ABO BG directly affects red blood cell (RBC) homeostasis through BG-dependent modulation of erythropoiesis at the microRNA level and corresponding transcription factors (TFs). Furthermore, it was suggested that ABO transcription may be regulated epigenetically. Since, histone modifications play a crucial role in the regulation of erythropoiesis we investigated the regulatory role of histone modifications for the ABO BG phenotype.
Hematopoietic stem cells carrying different ABO BG phenotype were differentiated into erythroid precursor cells for 5 days. Chromatin immunoprecipitation coupled with high-throughput sequencing analyses using antibodies against activating histone modifications H3K9ac, H3K27ac, and H3K4me3 were performed in triplicates.
On day five of erythroid differentiation, the number of blood group specific H3K9ac modifications in cells carrying BG B were around 10x and 5x higher compared to BG A and O, respectively. In contrast, the number of H3K4me3 modifications was increased in cells carrying BG A and O compared to BG B. Furthermore, H3K27ac modifications dominated in cells of BG O. Whereas, in cells carrying BG B an increased number of H3K9ac and H3K4me3 peaks were located in the gene body (particular in introns), in cells carrying BG A these modifications were predominantly located in the promotor-TSS (transcription start site) region (<1kb). H3K27ac modifications were less present independent of the BG phenotype, whereas in cells carrying BG B and O a higher number of peaks were found in intergenic regions. In cells of BG A H3K27ac modifications were more present in promotor-TSS regions.
Our data suggest for the first time that histone modifications are associated with the ABO BG resulting in differences in the regions that are accessible for the respective transcription factors. This might be an explanation for the blood group-dependent differences in the regulation of erythropoiesis. Further exploration of the epigenetic regulation of the ABO BG dependent modulation of erythropoiesis holds great potential for shedding light on various diseases, including myocardial infarction, thrombosis, and infection, where associations between incidence and the ABO blood group have been reported.
We have no conflict of interest.