ArticleThe Journal of biological chemistry2013
Functional specificity of CpG DNA-binding CXXC domains in mixed lineage leukemia.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- KMT2A degradation is observed in decitabine-responsive acute lymphoblastic leukemia cells.Molecular oncology · 2025Article
- Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation.Journal of molecular biology · 2024Review
- Direct targeted therapy for MLL-fusion-driven high-risk acute leukaemias.Clinical and translational medicine · 2022Article
- The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(6;11).Oncogene · 2021Article
- Structure, Activity and Function of the MLL2 (KMT2B) Protein Lysine Methyltransferase.Life (Basel, Switzerland) · 2021Review
- Understanding the interplay between CpG island-associated gene promoters and H3K4 methylation.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
- Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications.International journal of molecular sciences · 2019Review
- The survival analysis and oncogenic effects of CFP1 and 14-3-3 expression on gastric cancer.Cancer cell international · 2019Article
- The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin.Cell reports · 2017Article
- Distinct functions of histone H3, lysine 4 methyltransferases in normal and malignant hematopoiesis.Current opinion in hematology · 2017Review
- MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia.Cell reports · 2017Article
- SET/MLL family proteins in hematopoiesis and leukemia.International journal of hematology · 2017Review
- MLL1 and MLL1 fusion proteins have distinct functions in regulating leukemic transcription program.Cell discovery · 2016Article
- Hijacked in cancer: the KMT2 (MLL) family of methyltransferases.Nature reviews. Cancer · 2015Review
- The Cardiac Stress Response Factor Ms1 Can Bind to DNA and Has a Function in the Nucleus.PloS one · 2015Article
- Two decades of leukemia oncoprotein epistasis: the MLL1 paradigm for epigenetic deregulation in leukemia.Experimental hematology · 2014Review
- Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin.BMC genomics · 2013Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The MLL CXXC domain binds nonmethylated CpG-containing DNA and is essential for the oncogenic properties of MLL fusion proteins. To determine potential functional promiscuity of similar DNA binding domains, we replaced the MLL CXXC domain in the context of the leukemogenic MLL-AF9 fusion with CXXC domains from DNMT1, CGBP (CFP1), and MBD1, or with a methyl-CpG-binding domain (MBD) from MBD1. MLL(DNMT1 CXXC)-AF9 shows robust in vitro colony forming activity and in vivo leukemogenesis, similar to MLL-AF9. However, colony forming ability and leukemogenicity are abrogated in MLL-AF9 containing either the CGBP or MBD1 CXXC domains or the MBD1 MBD domain. Direct comparison of in vitro DNA binding affinity of the isolated CXXC or MBD domains demonstrated that MLL, DNMT1, and CGBP CXXC domains could each bind to unmethylated DNA but with differing affinity. In contrast, the isolated MBD1 CXXC and MBD1 MBD domains were unable to bind to the same DNA. However, all substituted domains still allowed targeting of the MLL fusions to the functionally important Hoxa9 locus in primary bone marrow progenitor cells. In addition to DNA binding activity, it was critical that specific CpG residues in the Hoxa9 locus were protected from methylation for leukemia development. This ultimately prevented histone 3 lysine 9 trimethylation (H3K9me3) of the locus and enabled Hoxa9 expression. These were properties shared by MLL and DNMT1 CXXC domains but not by CGBP CXXC or the other swapped fusions tested. We demonstrate that similar CXXC domains can be mechanistically distinguished by specificity of CpG nucleotides preferentially protected from DNA methylation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.