DKC1 is a transcriptional target of GATA1 and drives upregulation of telomerase activity in normal human erythroblasts.

DKC1 is a transcriptional target of GATA1 and drives upregulation of telomerase activity in normal human erythroblasts. Haematologica. 2019 Aug 14;: Authors: Richards LA, Kumari A, Knezevic K, Thoms JA, von Jonquieres G, Napier CE, Ali Z, O'Brien R, Marks-Bluth J, Maritz MF, Pickett HA, Morris J, Pimanda JE, MacKenzie KL Abstract Telomerase is a ribonucleoprotein complex that maintains the length and integrity of telomeres to enable ongoing cellular proliferation. Understanding the regulation of telomerase in hematopoietic cells is relevant to the pathogenesis of leukemia where telomerase is constitutively activated, as well as bone marrow failure syndromes that feature telomerase insufficiency. Past studies showing high levels of telomerase in human erythroblasts and a prevalence of anemia in disorders of telomerase insufficiency provide rationale for investigating telomerase regulation in erythroid cells. Here it is shown for the first time that the telomerase RNA-binding protein dyskerin (DKC1) is dramatically upregulated as human HSPCs commit to the erythroid lineage, driving an increase in telomerase activity in the presence of limiting amounts of TERT mRNA. Further, it is shown that upregulation of DKC1 was necessary for expansion of Glycophorin A+ (GLYA+) erythroblasts and sufficient to extend telomeres in erythroleukemia cells. Chromatin immunoprecipitation and reporter assays implicated GATA1-mediated transcriptional regulat...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research