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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / genetics
-
Cell Differentiation / drug effects
-
Chromobox Protein Homolog 5
-
Gene Expression Regulation, Neoplastic
-
HL-60 Cells
-
Histocompatibility Antigens / genetics
-
Histocompatibility Antigens / metabolism*
-
Histone-Lysine N-Methyltransferase / genetics
-
Histone-Lysine N-Methyltransferase / metabolism*
-
Humans
-
Janus Kinase 2 / biosynthesis
-
Janus Kinase 2 / metabolism*
-
K562 Cells
-
LIM Domain Proteins / genetics
-
Leukemia / metabolism*
-
Leukemia / pathology
-
Methylation
-
Phosphorylation
-
Promoter Regions, Genetic
-
Proto-Oncogene Proteins / genetics
-
Transcription, Genetic
-
Tretinoin / pharmacology
-
YY1 Transcription Factor / metabolism*
Substances
-
Adaptor Proteins, Signal Transducing
-
CBX5 protein, human
-
Histocompatibility Antigens
-
LIM Domain Proteins
-
LMO2 protein, human
-
Proto-Oncogene Proteins
-
YY1 Transcription Factor
-
YY1 protein, human
-
Chromobox Protein Homolog 5
-
Tretinoin
-
EHMT2 protein, human
-
Histone-Lysine N-Methyltransferase
-
JAK2 protein, human
-
Janus Kinase 2