KAT6B (MYST histone acetyltransferase (monocytic leukemia) 4)

2006-05-01   José Luis Vizmanos 

Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, 31008 Pamplona, Navarra, Espana

Identity

HGNC
LOCATION
10q22.2
IMAGE
Atlas Image
LEGEND
Genomic structure of MYST4. Black boxes indicate exons.
LOCUSID
ALIAS
GTPTS,MORF,MOZ2,MYST4,ZC2HC6B,qkf,querkopf
FUSION GENES

DNA/RNA

Description

18 exons spanning 206.0 Kb on 10q22.2. Transcription is from centromere to telomere.

Transcription

1 transcript

Proteins

Note

MYST4_HUMAN; Histone acetyltransferase MYST4, MYST protein 4, MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4, Histone acetyltransferase MOZ2, Monocytic leukemia zinc finger protein-related factor, or Histone acetyltransferase MORF.
Atlas Image
Schematic representation of MYST4 protein. H15 domain: domain in histone families 1 and 5; PHD zinc fingers: plant homeodomain (PHD) with a C4HC3-type motif, this domain is widely distributed in eukaryotes and it has been found in many chromatin regulatory factors; MOZ-SAS family region: this region has been suggested to be homologous to acetyltransferases but this similarity is not supported by sequence analysis.

Description

Histone acetyltransferase MYST4.

Localisation

Nucleous (probable).

Function

It is a histone acetyltransferase probably involved in both positive (N-terminus) and negative (C-terminus) regulation of transcription, maybe involved in cerebral cortex development, required for RUNX2-dependent transcriptional activation and ubiquitously expressed in adult human tissues.

Mutations

Somatic

MYST4 fusion genes in neoplasia t(10;16)(q22;p13) (see below) 5 MYST4-CREBBP 3 (previously known as MORF-CBP, MORF-CREBBP, or MYST4-CBP) fusion was first described in a 4-year-old girl with AML M5a without signs of erythrophagocytosis and several chromosome abnormalities. It was also described in an 84-year-old male without erythrophagocytosis and with this sole cytogenetic aberration. This suggested that the recurrent fusion gene could contribute directly to the development of the AML. This fusion gene was also described with a variant breakpoint in a 52-year-old japanese woman with a therapy-related myelodysplastic syndrome (t-MDS) and this sole translocation. A novel fusion variant was also described in an AML-M4 female patient with the t(10;16) (q22;p13) and a t(11;17)(q23;q21).

t(10;17)(q22;q21-q24). It has been observed that 5% of chromosomally abnormal uterine leiomyomata had rearrangements of 10q22, most of them with balanced translocations with a variety of partners in chromosomes 4, 6, or 12 in leiomyomata and chromosomes 7, 11, 17, or 18 in leiomyosarcomas. Previously the t(10;17) had been reported as the sole cytogenetic abnormality in one leiomyosarcoma and as part of a complex karyotype in another leiomyosarcoma.

FISH analysis of four uterine leiomyomata has revealed a breakpoint in the third intron of MYST4 after the H15 domain and before the PHD zinc finger domain. This disruption of MYST4 seems to be more 5 to the breakpoints reported in hematopoietic malignancies. In addition, in three of the four uterine leiomyomata, the10q22 rearrangement also involves a locus on 17q with probably the same breakpoint. This could suggest a cytogenetically distinct subgroup of uterine leiomyomata that could be also defined by a common phenotype.

Implicated in

Note
The t(10;16)(q22;p13) fusing MYST4 and CREBBP to generate a chimeric protein MYST4-CREBBP (previously known as MORF-CBP, MORF-CREBBP, or MYST4-CBP) is a very rare cytogenetic abnormality only described in 4 cases to date with AML M4/M5a and therapy-related MDS without signs of erythrophagocytosis; most of them with bad prognosis.

This translocation is related to t(8;16)(p11;p13) that fuses MYST3 to CREBBP (previously also known as MOZ-CREBBP or MOZ-CBP) also described in cases with AML/M4-M5 and therapy-related AML with a poor response to chemotherapy and frequently displaying erythrophagocytosis.

Disease
Described in two cases with AML M5, one case with AML M4 and one case with therapy-related MDS, all of them without signs of erythrophagocytosis (showed in the t(8;16), MYST3-CREBBP fusion).
Prognosis
poor.
Cytogenetics
t(10;16)(q22;p13), rarely as sole anomaly.
Hybrid gene
5 MYST4-CREBBP 3
Fusion protein
MYST4-CREBBP The putative MYST4-CREBBP fusion protein retains the zinc fingers, two nuclear localization signals, the HAT domain, and a portion of the acidic domain from MYST4, and most of the CREBBP protein, including its HAT domain.

Entity name
Rearrangements of 10q22 in uterine leiomyomata
Note
Some of the chromosomally abnormal uterine leiomyomata had rearrangements of 10q22, most of them with balanced translocations with a variety of partners in chromosomes 4, 6, or 12 in leiomyomata and chromosomes 7, 11, 17, or 18 in leiomyosarcomas. FISH analysis of some uterine leiomyomata has revealed a disruption of MYST4 between the H15 domain and the PHD zinc finger domain. In three cases the partner gene was a locus on 17q with probably the same breakpoint. This could delimit a distinct subgroup of uterine leiomyomata.
Prognosis
Unknown.
Cytogenetics
Rearrangements of 10q22, most of them with balanced translocations with chromosomes 4, 6, or 12 in leiomyomata and chromosomes 7, 11, 17, or 18 in leiomyosarcomas.
Hybrid gene
Several cases has shown disruption of MYST4, some of them with an unknown partner in 17q21-q24.
Fusion protein
Unknown.

Bibliography

Pubmed IDLast YearTitleAuthors
104972171999Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein.Champagne N et al
31632641988t(10;17) as the sole chromosome change in a uterine leiomyosarcoma.Dal Cin P et al
23544581990Chromosome aberrations in uterine smooth muscle tumors: potential diagnostic relevance of cytogenetic instability.Fletcher JA et al
125424852003A novel fusion variant of the MORF and CBP genes detected in therapy-related myelodysplastic syndrome with t(10;16)(q22;p13).Kojima K et al
153138932004Uterine leiomyomata with t(10;17) disrupt the histone acetyltransferase MORF.Moore SD et al
151473752004Variant MYST4-CBP gene fusion in a t(10;16) acute myeloid leukaemia.Murati A et al
111578022001Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13).Panagopoulos I et al
128931702003Expression, purification, and analysis of MOZ and MORF histone acetyltransferases.Pelletier N et al
147663402004Querkopf, a histone acetyltransferase, is essential for embryonic neurogenesis.Thomas T et al
166262842006MOZ fusion proteins in acute myeloid leukaemia.Troke PJ et al
125969092003The MYST family of histone acetyltransferases.Utley RT et al
126191642003t(10;16)(q22;p13) and MORF-CREBBP fusion is a recurrent event in acute myeloid leukemia.Vizmanos JL et al

Other Information

Locus ID:

NCBI: 23522
MIM: 605880
HGNC: 17582
Ensembl: ENSG00000156650

Variants:

dbSNP: 23522
ClinVar: 23522
TCGA: ENSG00000156650
COSMIC: KAT6B

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000156650ENST00000287239Q8WYB5
ENSG00000156650ENST00000372711Q8WYB5
ENSG00000156650ENST00000372714Q8WYB5
ENSG00000156650ENST00000372724Q8WYB5
ENSG00000156650ENST00000372725Q8WYB5
ENSG00000156650ENST00000604130A0A3B3IRN9
ENSG00000156650ENST00000647554A0A3B3ISD0
ENSG00000156650ENST00000647637A0A3B3IT63
ENSG00000156650ENST00000647642A0A3B3ITC3
ENSG00000156650ENST00000647666A0A3B3ISD5
ENSG00000156650ENST00000647890A0A3B3ITV5
ENSG00000156650ENST00000648048A0A3B3ISI1
ENSG00000156650ENST00000648159A0A3B3ISF5
ENSG00000156650ENST00000648369A0A3B3IRI4
ENSG00000156650ENST00000648370A0A3B3ITI0
ENSG00000156650ENST00000648483A0A3B3IUA4
ENSG00000156650ENST00000648539A0A3B3ITP3
ENSG00000156650ENST00000648696A0A3B3IRV4
ENSG00000156650ENST00000648725Q8WYB5
ENSG00000156650ENST00000648828A0A3B3ISX5
ENSG00000156650ENST00000648892Q8WYB5
ENSG00000156650ENST00000648899A0A3B3IS73
ENSG00000156650ENST00000649006Q8WYB5
ENSG00000156650ENST00000649119A0A3B3IU71
ENSG00000156650ENST00000649375A0A3B3IU93
ENSG00000156650ENST00000649442A0A3B3IU70
ENSG00000156650ENST00000649463Q8WYB5
ENSG00000156650ENST00000649657A0A3B3ISW3
ENSG00000156650ENST00000650048A0A3B3ITA4
ENSG00000156650ENST00000650232A0A3B3IT19
ENSG00000156650ENST00000650434A0A3B3ITP3

Expression (GTEx)

0
5
10
15
20

Pathways

PathwaySourceExternal ID
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
HATs acetylate histonesREACTOMER-HSA-3214847

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
187943582008Molecular architecture of quartet MOZ/MORF histone acetyltransferase complexes.79
163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.69
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
220779732011Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.51
222650142012Mutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndrome.40
218041882011Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice.39
230637132012Tandem PHD fingers of MORF/MOZ acetyltransferases display selectivity for acetylated histone H3 and are required for the association with chromatin.35
218807312011Recognition of unmodified histone H3 by the first PHD finger of bromodomain-PHD finger protein 2 provides insights into the regulation of histone acetyltransferases monocytic leukemic zinc-finger protein (MOZ) and MOZ-related factor (MORF).31
222650172012De novo mutations of the gene encoding the histone acetyltransferase KAT6B cause Genitopatellar syndrome.31
241509412014The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification.23

Citation

José Luis Vizmanos

KAT6B (MYST histone acetyltransferase (monocytic leukemia) 4)

Atlas Genet Cytogenet Oncol Haematol. 2006-05-01

Online version: http://atlasgeneticsoncology.org/gene/41488/kat6b-(myst-histone-acetyltransferase-(monocytic-leukemia)-4)