3-Deazaneplanocin A (DZNep), an Inhibitor of S-Adenosylmethionine-dependent Methyltransferase, Promotes Erythroid Differentiation

Abstract

Background: S-adenosylmethionine-dependent methyltransferase inhibitor, DZNep, targets the degradation of histone methyltransferase EZH2 that catalyzes H3K27 trimethylation.Results: DZNep induced erythroid-related genes, which may not be directly related to EZH2 inhibition but may be partly associated with reduced protein level of hematopoietic corepressor ETO2.Conclusion: DZNep has the capacity to induce erythroid differentiation.Significance: Our data may be exploited for therapeutic applications for hematological diseases, including anemia.

HDAC1,2 inhibition impairs EZH2- and BBAP- mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma

“…Low dose DZNep treatment did not affect bulk H3K27me3 levels in multiple myeloma and lung cancer cell lines [34, 35]. Additionally, 0.2-1μM DZNep treatment of K562 erythroid cells for 72h reduced cell viability, but global level of H3K27me3 remained unaffected even though Western blotting showed reduced EZH2 levels [36]. However, in this study, it was shown that DZNep treatment decreases H3K27me3 at select loci, such as, SLC4A1 and EPB42 , which are targets of the ETO2 co-repressor.…”

miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2

“…Though it was reported that PRC2 complex components including EZH2 was involved in epigenetic silencing of a subset of erythropoiesis-related genes [74,75], the cytoprotective role of EZH2 in erythroid cells under stress conditions remains largely unknown thus far. Here, we uncovered a direct regulation of EZH2 by Nrf2 through miR-214 in response to oxidative stress, as As treatment increased EZH2 protein concentration by suppressing miR-214 level, associated with resultant elevation of global H3K27me3 level.…”

Effect of 5-aminolevulinic acid on erythropoiesis: A preclinical in vitro characterization for the treatment of congenital sideroblastic anemia

“…SurePrint G3 Human GE 8 Â 60 K Microarrays (G4851B) (Agilent, Palo Alto, CA, USA) and Human Oligo chip 25 k (Toray, Tokyo, Japan) were used, respectively, for expression profiling of ALA-treated K562 cells and ALAS2-knockdowned HiDEP cells, as described previously [13]. Gene Ontology analysis was performed as previously described [13].…”

“…Western blotting was conducted as described previously [13,24]. Antibodies for ALAS2 (ab184964) and Actin (I-19) were purchased from Abcam (Cambridge, UK) and Santa Curz Biotechnology (Santa Cruz, CA, USA), respectively.…”