In the experiments in the article above, we used reagents supplied by Signalway Biotechnology (Pearland, TX, USA). At the time of publication, the corresponding author, Zhimin Lu, did not include a declaration of conflict of interest regarding Signalway Biotechnology. In the interest of transparency, Dr. Lu would like to ensure this relationship is included as part of the published paper going forward, in the form of the following statement: Zhimin Lu and his family members have a direct financial interest (100% equity) in Signalway Biotechnology that supplied Total RNA Rapid Extraction Kit, Thermo Reverse Transcription Kit, PCR Premixture, and antibodies recognizing EGFR pY1172, PKM1, PKM2, H3 pT11, p H3 pS10, and c-Myc used for the work reported in this paper.
Purpose of review
Histone H3, lysine 4 methylation (H3K4me) is one chromatin modification that defines distinct regulatory states of euchromatin. Mammals express 6 main histone methyltransferase enzymes (HMTs) that modify H3K4 by mono-, di-, or tri-methylation. Recent studies examine roles of some of these HMTs and their cofactors in hematopoiesis and leukemia. We discuss these emerging studies together with prior embryonic stem (ES) data revealing how these enzymes function.
Recent findings
Murine models have been employed to conditionally or constitutively knock out HMTs (MLL1/KMT2A, MLL2/KMT2B, MLL3/KMT2C, MLL4/KMT2D, SETD1A/KMT2F and SETD1B/KMT2G) as well as specific domains or partners of these enzymes in normal hematopoietic populations and in the context of hematologic malignancies. These studies demonstrate that global or gene-specific changes in H3K4 modification levels can be attributed to particular enzymes in particular tissues.
Summary
Loss-of-function studies indicate largely non-overlapping roles of the six H3K4 HMTs. These roles are not all necessarily due to differences in enzymatic activity and are not always accompanied by large global changes in histone modification. Both gain- and loss-of-function mutations in hematologic malignancy are restricted to MLL1 and MLL3/MLL4, but emerging data indicate that SETD1A/SETD1B and MLL2 can be critical in leukemia as well.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.