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EHMT1 and EHMT2 inhibition induce fetal hemoglobin expression [RNA-seq]

ABSTRACT: Using UNC0638 and genetic assays to inhibit EHMT1/2 and derepress fetal hemoglobin in adult hematopoietic cells. RNA-Seq in primary adult human erythroid cells treated with UNC0638 or the vehicle control (DMSO) in biological triplicates.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Homo sapiens

SUBMITTER: John Krill-Burger

PROVIDER: E-GEOD-71421 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression.

Renneville Aline A Van Galen Peter P Canver Matthew C MC McConkey Marie M Krill-Burger John M JM Dorfman David M DM Holson Edward B EB Bernstein Bradley E BE Orkin Stuart H SH Bauer Daniel E DE Ebert Benjamin L BL

Blood 20150828 16

Fetal hemoglobin (HbF, α2γ2) induction is a well-validated strategy for sickle cell disease (SCD) treatment. Using a small-molecule screen, we found that UNC0638, a selective inhibitor of EHMT1 and EHMT2 histone methyltransferases, induces γ-globin expression. EHMT1/2 catalyze mono- and dimethylation of lysine 9 on histone 3 (H3K9), raising the possibility that H3K9Me2, a repressive chromatin mark, plays a role in silencing γ-globin expression. In primary human adult erythroid cells, UNC0638 and ...[more]

PMID: 26320100

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