MYST4 (MYST histone acetyltransferase (monocytic leukemia) 4)

Identity

Other names	qkf
	MORF
	MOZ2
	FLJ90335
	KIAA0383
	querkopf
	DKFZp313G1618
	EC 2.3.1.- EC 2.3.1.48
Hugo	MYST4
Location	10q22.2
Local_order	ADK (adenosine kinase isoform a) is more centromeric. DUPD1 (dual specificity phosphatase and pro isomerase) is more telomeric.
	Genomic structure of MYST4. Black boxes indicate exons.

DNA/RNA

Description	18 exons spanning 206.0 Kb on 10q22.2. Transcription is from centromere to telomere.
Transcription	1 transcript

Protein

	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.

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.
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

Entity	t(10;16)(q22;p13)
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/Mutated Gene	5' MYST4-CREBBP 3'
Abnormal 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	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/Mutated Gene	Several cases has shown disruption of MYST4, some of them with an unknown partner in 17q21-q24.
Abnormal Protein	Unknown.

External links

	Nomenclature
Hugo	MYST4
GDB	MYST4
Entrez_Gene	MYST4  23522  MYST histone acetyltransferase (monocytic leukemia) 4
	Cards
Atlas	MYST4ID41488ch10q22
GeneCards	MYST4
Ensembl	MYST4 [Search_View]   ENSG00000156650 [Gene_View]
Genatlas	MYST4
GeneLynx	MYST4
eGenome	MYST4
euGene	23522
	Genomic and cartography
GoldenPath	MYST4  -  10q22.2   chr10:76256385-76462645 +  10q22.2   [Description]    (hg18-Mar_2006)
Ensembl	MYST4 - 10q22.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	MYST4
	Gene and transcription
Genbank	AA416904 [ ENTREZ ]
Genbank	AB002381 [ ENTREZ ]
Genbank	AF113514 [ ENTREZ ]
Genbank	AF119230 [ ENTREZ ]
Genbank	AF119231 [ ENTREZ ]
RefSeq	NM_012330 [ SRS ]    NM_012330 [ ENTREZ ]
RefSeq	AC_000053 [ SRS ]    AC_000053 [ ENTREZ ]
RefSeq	NC_000010 [ SRS ]    NC_000010 [ ENTREZ ]
RefSeq	NT_008583 [ SRS ]    NT_008583 [ ENTREZ ]
RefSeq	NW_924796 [ SRS ]    NW_924796 [ ENTREZ ]
AceView	MYST4 AceView - NCBI
Unigene	Hs.599543 [ SRS ]    Hs.599543 [ NCBI ]     HS599543 [ spliceNest ]
Fast-db	14179 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q8WYB5 [ SRS]    Q8WYB5 [ EXPASY ]     Q8WYB5 [ INTERPRO ]
Prosite	PS01359 ZF_PHD_1 [ SRS ]    PS01359 ZF_PHD_1 [ Expasy ]
Prosite	PS50016 ZF_PHD_2 [ SRS ]    PS50016 ZF_PHD_2 [ Expasy ]
Interpro	IPR005818 Histone_H1/H5 [ SRS ]    IPR005818 Histone_H1/H5 [ EBI ]
Interpro	IPR002717 MOZ_SAS [ SRS ]    IPR002717 MOZ_SAS [ EBI ]
Interpro	IPR011991 Wing_hlx_DNA_bd [ SRS ]    IPR011991 Wing_hlx_DNA_bd [ EBI ]
Interpro	IPR001965 Znf_PHD [ SRS ]    IPR001965 Znf_PHD [ EBI ]
Interpro	IPR013083 Znf_RING/FYVE/PHD [ SRS ]    IPR013083 Znf_RING/FYVE/PHD [ EBI ]
CluSTr	Q8WYB5
Pfam	PF01853 MOZ_SAS [ SRS ]    PF01853 MOZ_SAS [ Sanger ]    pfam01853 [ NCBI-CDD ]
Pfam	PF00628 PHD [ SRS ]    PF00628 PHD [ Sanger ]    pfam00628 [ NCBI-CDD ]
Smart	SM00526 H15 [EMBL]
Smart	SM00249 PHD [EMBL]
Blocks	Q8WYB5
HPRD	07065
	Protein Interaction databases
DIP	Q8WYB5
IntAct	Q8WYB5
	Polymorphism : SNP, mutations, diseases
OMIM	605880    [ map ]
GENECLINICS	605880
SNP	MYST4 [dbSNP-NCBI]
SNP	NM_012330 [SNP-NCI]
SNP	MYST4 [GeneSNPs - Utah]  MYST4] [HGBASE - SRS]
HAPMAP	MYST4 [HAPMAP]
HGMD	MYST4
	General knowledge
Family Browser	MYST4 [UCSC Family Browser]
SOURCE	NM_012330
SMD	Hs.599543
SAGE	Hs.599543
Enzyme	2.3.1.48 [ Enzyme-SRS ]   2.3.1.48 [ Brenda-SRS ]   2.3.1.48 [ KEGG ]   2.3.1.48 [ WIT ]
GO	nucleosome [Amigo]  nucleosome
GO	DNA binding [Amigo]  DNA binding
GO	histone acetyltransferase activity [Amigo]  histone acetyltransferase activity
GO	nucleus [Amigo]  nucleus
GO	nucleosome assembly [Amigo]  nucleosome assembly
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	transcription factor binding [Amigo]  transcription factor binding
GO	zinc ion binding [Amigo]  zinc ion binding
GO	acetyltransferase activity [Amigo]  acetyltransferase activity
GO	negative regulation of transcription [Amigo]  negative regulation of transcription
GO	transcription activator activity [Amigo]  transcription activator activity
GO	transcription repressor activity [Amigo]  transcription repressor activity
GO	chromatin modification [Amigo]  chromatin modification
GO	histone acetylation [Amigo]  histone acetylation
GO	transferase activity [Amigo]  transferase activity
GO	positive regulation of transcription [Amigo]  positive regulation of transcription
GO	metal ion binding [Amigo]  metal ion binding
KEGG	Valine, leucine and isoleucine degradation
KEGG	Tyrosine metabolism
KEGG	Phenylalanine metabolism
KEGG	Glycerophospholipid metabolism
KEGG	1- and 2-Methylnaphthalene degradation
KEGG	Benzoate degradation via CoA ligation
KEGG	Ethylbenzene degradation
KEGG	Limonene and pinene degradation
KEGG	Alkaloid biosynthesis II
PubGene	MYST4
TreeFam	MYST4
CTD	23522 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	MYST4 Related clones (RZPD - Berlin)
	PubMed
PubMed	13 Pubmed reference(s) in LocusLink

Bibliography

t(10;17) as the sole chromosome change in a uterine leiomyosarcoma.

Dal Cin P, Boghosian L, Crickard K, Sandberg AA

Cancer genetics and cytogenetics. 1988 ; 32 (2) : 263-266.

PMID 3163264

Chromosome aberrations in uterine smooth muscle tumors: potential diagnostic relevance of cytogenetic instability.

Fletcher JA, Morton CC, Pavelka K, Lage JM

Cancer research. 1990 ; 50 (13) : 4092-4097.

PMID 2354458

Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein.

Champagne N, Bertos NR, Pelletier N, Wang AH, Vezmar M, Yang Y, Heng HH, Yang XJ

The Journal of biological chemistry. 1999 ; 274 (40) : 28528-28536.

PMID 10497217

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, Billstrˆ�m R, Strˆ�mbeck B, Mitelman F, Johansson B

Human molecular genetics. 2001 ; 10 (4) : 395-404.

PMID 11157802

A novel fusion variant of the MORF and CBP genes detected in therapy-related myelodysplastic syndrome with t(10;16)(q22;p13).

Kojima K, Kaneda K, Yoshida C, Dansako H, Fujii N, Yano T, Shinagawa K, Yasukawa M, Fujita S, Tanimoto M

British journal of haematology. 2003 ; 120 (2) : 271-273.

PMID 12542485

Expression, purification, and analysis of MOZ and MORF histone acetyltransferases.

Pelletier N, Champagne N, Lim H, Yang XJ

Methods (San Diego, Calif.). 2003 ; 31 (1) : 24-32.

PMID 12893170

The MYST family of histone acetyltransferases.

Utley RT, Cˆ¥tˆ© J

Current topics in microbiology and immunology. 2003 ; 274 : 203-236.

PMID 12596909

t(10;16)(q22;p13) and MORF-CREBBP fusion is a recurrent event in acute myeloid leukemia.

Vizmanos JL, Larrˆ°yoz MJ, Lahortiga I, Floristˆ°n F, Alvarez C, Odero MD, Novo FJ, Calasanz MJ

Genes, chromosomes & cancer. 2003 ; 36 (4) : 402-405.

PMID 12619164

Uterine leiomyomata with t(10;17) disrupt the histone acetyltransferase MORF.

Moore SD, Herrick SR, Ince TA, Kleinman MS, Cin PD, Morton CC, Quade BJ

Cancer research. 2004 ; 64 (16) : 5570-5577.

PMID 15313893

Variant MYST4-CBP gene fusion in a t(10;16) acute myeloid leukaemia.

Murati A, Adˆ©laˆØde J, Mozziconacci MJ, Popovici C, Carbuccia N, Letessier A, Birg F, Birnbaum D, Chaffanet M

British journal of haematology. 2004 ; 125 (5) : 601-604.

PMID 15147375

Querkopf, a histone acetyltransferase, is essential for embryonic neurogenesis.

Thomas T, Voss AK

Frontiers in bioscience : a journal and virtual library. 2004 ; 9 : 24-31.

PMID 14766340

MOZ fusion proteins in acute myeloid leukaemia.

Troke PJ, Kindle KB, Collins HM, Heery DM

Biochemical Society symposium. 2006 : 23-39.

PMID 16626284

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	05-2006	José Luis Vizmanos
		Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, 31008 Pamplona, Navarra, Espana

Citation

This paper should be referenced as such :

Vizmanos JL . MYST4 (MYST histone acetyltransferase (monocytic leukemia) 4). Atlas Genet Cytogenet Oncol Haematol. May 2006 . URL : http://AtlasGeneticsOncology.org/Genes/MYST4ID41488ch10q22.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:25:20 2008