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KAT6A  -  K(lysine) acetyltransferase 6A

Homo sapiens

Synonyms: Histone acetyltransferase KAT6A, MOZ, MOZ, YBF2/SAS3, SAS2 and TIP60 protein 3, MYST-3, MYST3, ...
 
 
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Disease relevance of MYST3

 

High impact information on MYST3

  • We suggest that MOZ may represent a chromatin-associated acetyltransferase, and raise the possibility that a dominant MOZ-CBP fusion protein could mediate leukaemogenesis via aberrant chromatin acetylation [6].
  • At the chromosome 8 breakpoint we identify a novel gene, MOZ, which encodes a 2,004-amino-acid protein characterized by two C4HC3 zinc fingers and a single C2HC zinc finger in conjunction with a putative acetyltransferase signature [6].
  • Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells [7].
  • Sas3 is the yeast homolog of the human MOZ oncogene [8].
  • On the other hand, the MOZ-CBP fusion protein, which is created by the t(8;16) translocation associated with acute monocytic leukemia, inhibits AML1-mediated transcription and differentiation of M1 cells [9].
 

Biological context of MYST3

 

Anatomical context of MYST3

 

Associations of MYST3 with chemical compounds

  • MOZ itself is a 2004-residue protein containing a putative acetyl CoA-binding motif, so it was hypothesized that MOZ is a HAT [15].
 

Regulatory relationships of MYST3

  • We further demonstrate that MOZ can activate the MIP-1alpha promoter and that this activation is largely dependent upon the proximal RUNX site [16].
 

Other interactions of MYST3

 

Analytical, diagnostic and therapeutic context of MYST3

  • We showed by Southern blot the rearrangement of the MOZ gene, and cloned the fusion transcripts in one patient carrying the t(8;22) by reverse transcription-polymerase chain reaction using MOZ- and p300-specific primers [17].
  • In addition, fluorescence in situ hybridization analysis suggested a rearrangement in the monocytic leukemia zinc finger (MOZ) gene, located in the 8p11 region of chromosome 8 [19].
  • The newly designed single-round PCR provides a simple tool for the molecular confirmation of MOZ/CBP rearrangement [20].
  • RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications [21].
  • The t(8;16)(p11;p13), which is strongly associated with acute myeloid leukemia (AML) displaying monocytic differentiation, erythrophagocytosis by the leukemic cells, and a poor response to chemotherapy, fuses the MOZ gene (8p11) with the CBP gene (16p13) [22].

References

  1. Identification and characterization of ASXL3 gene in silico. Katoh, M., Katoh, M. Int. J. Oncol. (2004) [Pubmed]
  2. Acute mixed lineage leukemia with an inv(8)(p11q13) resulting in fusion of the genes for MOZ and TIF2. Liang, J., Prouty, L., Williams, B.J., Dayton, M.A., Blanchard, K.L. Blood (1998) [Pubmed]
  3. A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. Carapeti, M., Aguiar, R.C., Goldman, J.M., Cross, N.C. Blood (1998) [Pubmed]
  4. Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13). Panagopoulos, I., Fioretos, T., Isaksson, M., Samuelsson, U., Billström, R., Strömbeck, B., Mitelman, F., Johansson, B. Hum. Mol. Genet. (2001) [Pubmed]
  5. A further case of acute myelomonocytic leukemia with inv(8) chromosomal rearrangement and MOZ-NCOA2 gene fusion. Murati, A., Adélaïde, J., Popovici, C., Mozziconacci, M.J., Arnoulet, C., Lafage-Pochitaloff, M., Sainty, D., Birnbaum, D., Chaffanet, M. Int. J. Mol. Med. (2003) [Pubmed]
  6. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Borrow, J., Stanton, V.P., Andresen, J.M., Becher, R., Behm, F.G., Chaganti, R.S., Civin, C.I., Disteche, C., Dubé, I., Frischauf, A.M., Horsman, D., Mitelman, F., Volinia, S., Watmore, A.E., Housman, D.E. Nat. Genet. (1996) [Pubmed]
  7. Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells. Thomas, T., Corcoran, L.M., Gugasyan, R., Dixon, M.P., Brodnicki, T., Nutt, S.L., Metcalf, D., Voss, A.K. Genes Dev. (2006) [Pubmed]
  8. The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex. John, S., Howe, L., Tafrov, S.T., Grant, P.A., Sternglanz, R., Workman, J.L. Genes Dev. (2000) [Pubmed]
  9. Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. Kitabayashi, I., Aikawa, Y., Nguyen, L.A., Yokoyama, A., Ohki, M. EMBO J. (2001) [Pubmed]
  10. MOZ fusion proteins in acute myeloid leukaemia. Troke, P.J., Kindle, K.B., Collins, H.M., Heery, D.M. Biochem. Soc. Symp. (2006) [Pubmed]
  11. MOZ-TIF2 alters cofactor recruitment and histone modification at the RARbeta2 promoter: differential effects of MOZ fusion proteins on CBP- and MOZ-dependent activators. Collins, H.M., Kindle, K.B., Matsuda, S., Ryan, C., Troke, P.J., Kalkhoven, E., Heery, D.M. J. Biol. Chem. (2006) [Pubmed]
  12. MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. Pelletier, N., Champagne, N., Stifani, S., Yang, X.J. Oncogene (2002) [Pubmed]
  13. Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement. Aguiar, R.C., Chase, A., Coulthard, S., Macdonald, D.H., Carapeti, M., Reiter, A., Sohal, J., Lennard, A., Goldman, J.M., Cross, N.C. Blood (1997) [Pubmed]
  14. moz regulates Hox expression and pharyngeal segmental identity in zebrafish. Miller, C.T., Maves, L., Kimmel, C.B. Development (2004) [Pubmed]
  15. The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase. Champagne, N., Pelletier, N., Yang, X.J. Oncogene (2001) [Pubmed]
  16. Transcriptional regulation of the human MIP-1alpha promoter by RUNX1 and MOZ. Bristow, C.A., Shore, P. Nucleic Acids Res. (2003) [Pubmed]
  17. MOZ is fused to p300 in an acute monocytic leukemia with t(8;22). Chaffanet, M., Gressin, L., Preudhomme, C., Soenen-Cornu, V., Birnbaum, D., Pébusque, M.J. Genes Chromosomes Cancer (2000) [Pubmed]
  18. Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein. Champagne, N., Bertos, N.R., Pelletier, N., Wang, A.H., Vezmar, M., Yang, Y., Heng, H.H., Yang, X.J. J. Biol. Chem. (1999) [Pubmed]
  19. Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11). Imamura, T., Kakazu, N., Hibi, S., Morimoto, A., Fukushima, Y., Ijuin, I., Hada, S., Kitabayashi, I., Abe, T., Imashuku, S. Genes Chromosomes Cancer (2003) [Pubmed]
  20. Type I MOZ/CBP (MYST3/CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation. Rozman, M., Camós, M., Colomer, D., Villamor, N., Esteve, J., Costa, D., Carrió, A., Aymerich, M., Aguilar, J.L., Domingo, A., Solé, F., Gomis, F., Florensa, L., Montserrat, E., Campo, E. Genes Chromosomes Cancer (2004) [Pubmed]
  21. RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications. Schmidt, H.H., Strehl, S., Thaler, D., Strunk, D., Sill, H., Linkesch, W., Jäger, U., Sperr, W., Greinix, H.T., König, M., Emberger, W., Haas, O.A. Leukemia (2004) [Pubmed]
  22. Genomic characterization of MOZ/CBP and CBP/MOZ chimeras in acute myeloid leukemia suggests the involvement of a damage-repair mechanism in the origin of the t(8;16)(p11;p13). Panagopoulos, I., Isaksson, M., Lindvall, C., Hagemeijer, A., Mitelman, F., Johansson, B. Genes Chromosomes Cancer (2003) [Pubmed]
 
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