ABSTRACT
Histone methylation at specific lysine residues is a crucial regulatory process in transcriptional regulation. Using chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis, we found that the H3K9-me2 target gene JAK2 was an important factor during differentiation of the HL-60 promyelocytic leukemia cell line by all-trans-retinoic acid (ATRA) treatment. Here, we report that the H3K9 methyltransferase G9a negatively regulated JAK2 transcription in histone methyltransferase activity and in a YY1-dependent manner during ATRA-mediated leukemia cell differentiation. We found that G9a knockdown repressed ATRA-mediated HL-60 cell differentiation. We demonstrated that G9a interacts with YY1 and is recruited to the JAK2 promoter along with corepressors, including histone deacetylase, that induced H3K9-me2. Repression of JAK2 transcription by G9a decreased H3Y41 phosphorylation and promoted inhibition of the recently identified JAK2-H3Y41P-HP1α pathway-mediated leukemogenesis.
Free PMC Article
Negative regulation of JAK2 by H3K9 methyltransferase G9a in leukemia
Riferimento:
Mol Cell Biol. 2012 Sep;32(18):3681-94.
Autori:
Son HJ, Kim JY, Hahn Y, Seo SB.
Fonte:
Mol Cell Biol. 2012 Sep;32(18):3681-94.
Anno:
2012
Azione:
Il gene bersaglio JAK2 è un fattore importante nel corso del differenziamento della linea cellulare di leucemia promielocitica dovuto al trattamento con acido all-trans-retinoico (ATRA).
Target:
ATRA/leucemia promielo
Sostanze: