Alternative titles; symbols
HGNC Approved Gene Symbol: KAT7
Cytogenetic location: 17q21.33 Genomic coordinates (GRCh38) : 17:49,788,681-49,835,026 (from NCBI)
Using yeast 2-hybrid analysis with ORCL1 (601902), the largest subunit of the origin recognition complex, as bait, Iizuka and Stillman (1999) identified MYST2, which they called HBO1, from a HeLa cell cDNA library. MYST2 encodes a 611-amino acid protein with a predicted molecular mass of 83 kD. MYST2 contains an N-terminal serine-rich region, and a C-terminal MYST domain that includes a putative acetyl-CoA-binding domain. Northern blot analysis showed ubiquitous expression of a MYST2 transcript, with high expression levels in ovarian tissue. The in vitro and in vivo binding of ORC1 with MYST2 was confirmed by a variety of immunoprecipitation assays.
Using yeast 2-hybrid analysis with human androgen receptor (AR; 313700) as bait, Sharma et al. (2000) identified MYST2. The in vitro and in vivo binding of AR with MYST2 was confirmed by a variety of immunoprecipitation assays, and deletion construct experiments mapped the AR-interaction domain to the C terminus of MYST2. Northern blot analysis detected ubiquitous expression of a 3.6-kb MYST2 transcript, at high levels in testis, and also demonstrated MYST2 expression in all 6 prostate cancer cell lines tested. Immunofluorescence analysis of MYST2-transfected CV-1 (monkey kidney) and PC-3 (human prostate) cells showed that MYST2 localizes to the nucleus, whether or not dihydrotestosterone is present. (DHT).
Stumpf (2020) mapped the KAT7 gene to chromosome 17q21.33 based on an alignment of the KAT7 sequence (GenBank BC032640) with the genomic sequence (GRCh38).
Using luciferase reporter assays, Sharma et al. (2000) showed that the N-terminal portion of MYST2 containing the serine-rich domain acts as a transcriptional inhibitor. Transient transfection assays showed that MYST2 inhibited AR-mediated transactivation of reporter constructs in CV-1 and PC-3 cells.
Using MYST2 immunoprecipitated from 293 cells, Iizuka and Stillman (1999) performed a variety of assays showing that MYST2 is part of a multisubunit complex that can acetylate histones H3 and H4.
MacPherson et al. (2020) screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of leukemia stem cells (LSCs). MacPherson et al. (2020) identified the MYST acetyltransferase HBO1 and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, they identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 (see 602810) at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes, including Hoxa9 (142956) and Hoxa10 (142957), that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, MacPherson et al. (2020) developed a highly potent small-molecule inhibitor of HBO1 and demonstrated its mode of activity as a competitive analog of acetyl-CoA. Inhibition of HBO1 phenocopied the genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients.
Iizuka, M., Stillman, B. Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein. J. Biol. Chem. 274: 23027-23034, 1999. [PubMed: 10438470] [Full Text: https://doi.org/10.1074/jbc.274.33.23027]
MacPherson, L., Anokye, J., Yeung, M. M., Lam, E. Y. N., Chan, Y.-C., Weng, C.-F., Yeh, P., Knezevic, K., Butler, M. S., Hoegl, A., Chan, K.-L., Burr, M. L., and 36 others. HBO1 is required for the maintenance of leukaemia stem cells. Nature 577: 266-270, 2020. [PubMed: 31827282] [Full Text: https://doi.org/10.1038/s41586-019-1835-6]
Sharma, M., Zarnegar, M., Li, X., Lim, B., Sun, Z. Androgen receptor interacts with a novel MYST protein, HBO1. J. Biol. Chem. 275: 35200-35208, 2000. [PubMed: 10930412] [Full Text: https://doi.org/10.1074/jbc.M004838200]
Stumpf, A. M. Personal Communication. Baltimore, Md. 06/09/2020.