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Negative regulation of JAK2 by H3K9 methyltransferase G9a in leukemia.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2012 Sep; Vol. 32 (18), pp. 3681-94. Date of Electronic Publication: 2012 Jul 16. - Publication Year :
- 2012
-
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.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Cell Differentiation drug effects
Chromobox Protein Homolog 5
Gene Expression Regulation, Neoplastic
HL-60 Cells
Histocompatibility Antigens genetics
Histone-Lysine N-Methyltransferase genetics
Humans
Janus Kinase 2 biosynthesis
K562 Cells
LIM Domain Proteins genetics
Leukemia pathology
Methylation
Phosphorylation
Promoter Regions, Genetic
Proto-Oncogene Proteins genetics
Transcription, Genetic
Tretinoin pharmacology
Histocompatibility Antigens metabolism
Histone-Lysine N-Methyltransferase metabolism
Janus Kinase 2 metabolism
Leukemia metabolism
YY1 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 32
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 22801367
- Full Text :
- https://doi.org/10.1128/MCB.00673-12