KMT2A
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| Location (UCSC) | Chr 11: 118.44 – 118.53 Mb | Chr 9: 44.71 – 44.79 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Histone-lysine N-methyltransferase 2A, also known as acute lymphoblastic leukemia 1 (ALL-1), myeloid/lymphoid or mixed-lineage leukemia 1 (MLL1), or zinc finger protein HRX (HRX), is an enzyme that in humans is encoded by the KMT2A gene.[5]
MLL1 is a histone
Function
Transcriptional regulation
KMT2A gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and
Transcriptome profiling after deletion of MLL1 in cortical neurons revealed decreased promoter-bound H3K4me3 peaks at 318 genes, with 31 of these having significantly decreased expression and promoter binding.[10] Among them were Meis2, a homeobox transcription factor critical for development of forebrain neurons[11][12] and Satb2, a protein involved in neuronal differentiation.[13]
Multiple chromosomal translocations involving this gene are the cause of certain
Cognition and emotion
MLL1 has been shown to be an important epigenetic regulator of complex behaviors. Rodent models of MLL1 dysfunction in forebrain neurons showed that conditional deletion results in elevated anxiety and defective cognition. Prefrontal cortex-specific knockout of MLL1 results in the same phenotypes, as well as working memory deficits.[10]
Stem cells
MLL1 has been found to be an important regulator of
Structure
Gene
KMT2A gene has 37
Protein
KMT2A has over a dozen binding partners and is cleaved into two pieces, a larger N-terminal fragment, involved in gene repression, and a smaller C-terminal fragment, which is a transcriptional activator.[16] The cleavage, followed by the association of the two fragments, is necessary for KMT2A to be fully active. Like many other methyltransferases, the KMT2 family members exist in multisubunit nuclear complexes (human COMPASS), where other subunits also mediate the enzymatic activity.[17]
Clinical significance
Abnormal H3K4 trimethylation has been implicated in several neurological disorders such as autism.
MLL1 is required for the expression of senescence-associated secretory phenotype (SASP)-related genes and promotes increased inflammation.[21]
Rearrangements of the MLL1 gene are associated with aggressive acute leukemias, both lymphoblastic and myeloid.[22] Despite being an aggressive leukemia, the MLL1 rearranged sub-type had the lowest mutation rates reported for any cancer.[23]
Mutations in MLL1 cause
Interactions
MLL (gene) has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000118058 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000002028 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 1720549.
- PMID 11259575.
- PMID 21847010.
- PMID 16951254.
- PMID 12482972.
- ^ PMID 25834037.
- S2CID 5166430.
- S2CID 21973035.
- S2CID 9248058.
- ^ a b "Entrez Gene: KMT2A lysine (K)-specific methyltransferase 2A".
- PMID 26996599.
- PMID 12393701.
- PMID 22500810.
- ^ PMID 22065254.
- ^ PMID 17942719.
- PMID 25135975.
- PMID 27259204.
- PMID 15941828.
- ^ PMID 25730765.
- S2CID 20957397.
- ^ PMID 15199122.
- PMID 12205094.
- PMID 11259575.
- ^ PMID 12829790.
- PMID 11313484.
- PMID 10490642.
Further reading
- Marschalek R, Nilson I, Löchner K, Greim R, Siegler G, Greil J, et al. (November 1997). "The structure of the human ALL-1/MLL/HRX gene". Leukemia & Lymphoma. 27 (5–6): 417–28. PMID 9477123.
- Eguchi M, Eguchi-Ishimae M, Greaves M (December 2003). "The role of the MLL gene in infant leukemia". International Journal of Hematology. 78 (5): 390–401. S2CID 39901963.
- Daser A, Rabbitts TH (May 2004). "Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis". Genes & Development. 18 (9): 965–74. PMID 15132992.
- Li ZY, Liu DP, Liang CC (February 2005). "New insight into the molecular mechanisms of MLL-associated leukemia". Leukemia. 19 (2): 183–90. PMID 15618964.
- Douet-Guilbert N, Morel F, Le Bris MJ, Sassolas B, Giroux JD, De Braekeleer M (January 2005). "Rearrangement of MLL in a patient with congenital acute monoblastic leukemia and granulocytic sarcoma associated with a t(1;11)(p36;q23) translocation". Leukemia & Lymphoma. 46 (1): 143–6. S2CID 6686086.
External links
- MLL OMIM Entry: MYELOID/LYMPHOID OR MIXED LINEAGE LEUKEMIA GENE; MLL
- MLL+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Gene MLL on the Atlas of Genetics and Oncology
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