Literature summary extracted from

Voss, A.K.; Thomas, T.
MYST family histone acetyltransferases take center stage in stem cells and development (2009), Bioessays, 31, 1050-1061.

Cloned(Commentary)

EC Number	Cloned (Comment)	Organism
2.3.1.48	expression of Tip60 in H-1299 human lung carcinoma cells, leads to increased c-Myc protein stability in the transfected cells	Mus musculus

Protein Variants

EC Number	Protein Variants	Comment	Organism
2.3.1.48	additional information	Both an enok null allele and a point mutation in the zinc finger of the MYST histone acetyltransferase domain cause an arrest in neuroblast proliferation. Enok mutation also results in a slow, but steady decline of egg production over time. However, no difference occurs in the proliferation of wing disk cells. Effects of mutating mof in flies are certainly most pronounced at and most relevant to the male X chromosome. Null mutation of the Hbo1 homologue in Drosophila melanogaster, chameau, leads to lethality at the pupal stage. Haploinsufficiency for chameau leads to defects in position effect variegation, in polycomb group protein mediated repression of homeotic genes and consequent homeotic transformation in thoracic and abdominal segments. Compound heterozygous flies for chameau and the PcG genes polycomb, polyhomeotic, or a mutation in a polycomb response element, Mcp, show more pronounced homeotic transformation than heterozygotes of the PcG genes alone. Depletion of Tip60 by RNAi leads to developmental lethality before or at the early pupal stage	Drosophila melanogaster
2.3.1.48	additional information	both male and female Ham1:Ham2 double-mutant gametophytes show abnormal development. Male double-mutant microspore mother cells and female megaspore mother cells undergo meiosis normally. Subsequently, both male and female gametophytes fail at the first post-meiotic, mitotic divisions. Fertile male pollen grains are still formed, although the lack of post-meiotic pollen mitosis I and II leads to fewer Ham1:Ham2 double-mutant pollen grains. Failure of the first post-meiotic, mitotic divisions in the female megagametogenesis, however, results in infertile Ham1:Ham2 double-mutant ovules	Arabidopsis thaliana
2.3.1.48	additional information	effects of sas2 mutation in yeast are quite specific to the euchromatin/heterochromatin boundary	Saccharomyces cerevisiae
2.3.1.48	additional information	loss of function of Moz causes defects in the hematopoietic stem cell compartment. Generation of different Moz mutant alleles with similar consequences for the hematopoietic system, phenotypes, overview. Qkf gt/gt mutants that survive to weaning age, which are less than 50% on an inbred 129Sv/Pas background, are smaller than littermate controls, have craniofacial abnormalities, skeletal abnormalities, and a disproportional reduction in the size of the cerebral cortex. Developing Qkf gt/gt mutant forebrain at embryonic day 11.5 contains fewer cerebrocortical progenitor cells, the cerebral cortex primordium, the cortical plate, contains fewer neurons and is reduced in size at embryonic days 13.5, 15.5, and 17.5. Mof mutant mouse embryos arrest in development at the blastocyst stage. RNAi screening in mouse embryonic stem cells reveals that Tip60 is required for pluripotency, and genome-wide expression analysis of Tip60-depleted embryonic stem cells suggests that Tip60 represses a large number of genes that are expressed during differentiation. Tip60 mutant mouse embryos die before implantation	Mus musculus
2.3.1.48	additional information	rather than leading to developmental arrest or lethality, RNAi knockdown of Tip60 in Caenorhabditis elegans leads to a recruitment of six instead of three cells into the vulval cell fate, the multivulva phenotype	Caenorhabditis elegans
2.3.1.48	additional information	RNAi depletion of HBO1 in 293-T cells results in an accumulation of cells in S phase of the cell cycle	Homo sapiens
2.3.1.48	additional information	zebrafish homozygous for ENU mutations in the zMoz gene exhibit pharyngeal arch segment identity defects extending to skeletal and nervous system elements of the head. Expression levels of Hox genes in the head region are reduced in zMoz mutants	Danio rerio

Localization

EC Number	Localization	Comment	Organism	GeneOntology No.	Textmining
2.3.1.48	autosome	-	Drosophila melanogaster	30849	-
2.3.1.48	nucleus	-	Drosophila melanogaster	5634	-
2.3.1.48	nucleus	-	Mus musculus	5634	-
2.3.1.48	nucleus	-	Homo sapiens	5634	-
2.3.1.48	nucleus	-	Saccharomyces cerevisiae	5634	-
2.3.1.48	nucleus	-	Arabidopsis thaliana	5634	-
2.3.1.48	nucleus	-	Caenorhabditis elegans	5634	-
2.3.1.48	nucleus	-	Danio rerio	5634	-

Natural Substrates/ Products (Substrates)

EC Number	Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
2.3.1.48	acetyl-CoA + c-Myc	Mus musculus	acetylation by Tip60 increases c-Myc protein stability in transfected H-1299 human lung carcinoma cells	CoA + acetylated c-Myc	-	?
2.3.1.48	acetyl-CoA + histone	Saccharomyces cerevisiae	histone acetylation on Lys16 by Sas2	CoA + acetylhistone	-	?
2.3.1.48	acetyl-CoA + histone H3	Homo sapiens	-	CoA + acetylhistone H3	-	?
2.3.1.48	acetyl-CoA + histone H4	Homo sapiens	-	CoA + acetylhistone H4	-	?
2.3.1.48	acetyl-CoA + histone H4	Drosophila melanogaster	Mof is required for sex chromosome dosage compensation acting in the MSL complex, which also contains Msl1-3, Mle, and RNA, to acetylate H4K16 and to increase gene transcription from the single male X chromosome	CoA + acetylhistone H4	-	?
2.3.1.48	acetyl-CoA + histone H4	Mus musculus	Mof is solely responsible for H4K16 acetylation in mouse blastocysts. Tip60 plays essential roles in cell cycle progression in vitro	CoA + acetylhistone H4	-	?
2.3.1.48	additional information	Danio rerio	a homologue of Moz, zMoz, occurs in zebrafish to perform a potential Moz function in the trunk region	?	-	?
2.3.1.48	additional information	Homo sapiens	HBO1 occurs as a component of a multiprotein complex with histone H3 and H4 acetyltransferase activity in 293 cells. The mammalian complex corresponding to the yeast NuA4 complex contains the MYST HAT Tip60	?	-	?
2.3.1.48	additional information	Saccharomyces cerevisiae	HBO1, Sas2 and Sas3 are involved in transcriptional repression enhancing Sir1-mediated epigenetic gene silencing. NuA3 and NuA4 complexes contain the MYST HATs Sas3 and Esa1, respectively. Sas2 histone acetylation of H4K16 opposed by Sir2 deacetylation of H4K16 at the euchromatin/heterochromatin interface maintains the boundary between regions of transcriptionally active and silent telomeric chromatin. Esa1 plays a role in maintaining the integrity of the DNA, rather than open chromatin structure and high-level transcriptional activity	?	-	?
2.3.1.48	additional information	Mus musculus	the mammalian complex corresponding to the yeast NuA4 complex contains the MYST HAT Tip60. Myc recruits the Tip60 complex to the chromatin in Rat1 wild-type cells, but not in Rat1 Myc mutant cells. Hbo1 appears to function predominantly in transcriptional repression	?	-	?
2.3.1.48	additional information	Caenorhabditis elegans	Tip60, in complex with homologues of the mammalian Tip60 complex, exhibits functional redundancy with two other groups of genes, known as synthetic multivulva A and B genes, synMUV. Therefore, the genes encoding proteins of the Tip60 complex are termed class C synMUV genes. SynMUV A and B counteract EGF to Ras to MAPK signaling and the Tip60 complex is a chromatin-modifying complex	?	-	?
2.3.1.48	additional information	Danio rerio zMoz	a homologue of Moz, zMoz, occurs in zebrafish to perform a potential Moz function in the trunk region	?	-	?

Organism

EC Number	Organism	UniProt	Comment	Textmining
2.3.1.48	Arabidopsis thaliana	-	genes ham1 and ham2	-
2.3.1.48	Caenorhabditis elegans	-	-	-
2.3.1.48	Danio rerio	-	zMoz	-
2.3.1.48	Danio rerio zMoz	-	zMoz	-
2.3.1.48	Drosophila melanogaster	-	HBO1, Mof, Enok, and chameau	-
2.3.1.48	Homo sapiens	-	gene Hbo1	-
2.3.1.48	Mus musculus	-	MNof, Tip60, Qkf, Moz, and Morf	-
2.3.1.48	Saccharomyces cerevisiae	-	-	-

Source Tissue

EC Number	Source Tissue	Comment	Organism	Textmining
2.3.1.48	blastocyst	-	Mus musculus	-
2.3.1.48	brain	HBO1	Homo sapiens	-
2.3.1.48	brain	mushroom bodies, expression of Enok	Drosophila melanogaster	-
2.3.1.48	brain	the Qkf gene, in addition to being strongly expressed in the developing cerebral cortex and in adult neural stem cells, is also expressed in post-mitotic cells such as neurons	Mus musculus	-
2.3.1.48	forebrain	Qkf/Morf	Mus musculus	-
2.3.1.48	germ cell	-	Mus musculus	-
2.3.1.48	head	zMoz expression is restricted to the zebrafish head	Danio rerio	-
2.3.1.48	HEK-293 cell	-	Homo sapiens	-
2.3.1.48	liver	fetal, expression of Moz	Mus musculus	-
2.3.1.48	additional information	Moz gene is expressed throughout the developing embryo and in most adult organs	Mus musculus	-
2.3.1.48	neuroblast	-	Drosophila melanogaster	-
2.3.1.48	neuron	the Qkf gene, in addition to being strongly expressed in the developing cerebral cortex and in adult neural stem cells, is also expressed in post-mitotic cells such as neurons	Mus musculus	-
2.3.1.48	osteoblast	-	Mus musculus	-
2.3.1.48	ovarian follicle	-	Drosophila melanogaster	-
2.3.1.48	testis	HBO1	Homo sapiens	-

Substrates and Products (Substrate)

EC Number	Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
2.3.1.48	acetyl-CoA + c-Myc	acetylation by Tip60 increases c-Myc protein stability in transfected H-1299 human lung carcinoma cells	Mus musculus	CoA + acetylated c-Myc	-	?
2.3.1.48	acetyl-CoA + c-Myc	acetylation by Tip60	Mus musculus	CoA + acetylated c-Myc	-	?
2.3.1.48	acetyl-CoA + histone	histone acetylation on Lys16 by Sas2	Saccharomyces cerevisiae	CoA + acetylhistone	-	?
2.3.1.48	acetyl-CoA + histone H3	-	Homo sapiens	CoA + acetylhistone H3	-	?
2.3.1.48	acetyl-CoA + histone H4	-	Homo sapiens	CoA + acetylhistone H4	-	?
2.3.1.48	acetyl-CoA + histone H4	Mof is required for sex chromosome dosage compensation acting in the MSL complex, which also contains Msl1-3, Mle, and RNA, to acetylate H4K16 and to increase gene transcription from the single male X chromosome	Drosophila melanogaster	CoA + acetylhistone H4	-	?
2.3.1.48	acetyl-CoA + histone H4	Mof is solely responsible for H4K16 acetylation in mouse blastocysts. Tip60 plays essential roles in cell cycle progression in vitro	Mus musculus	CoA + acetylhistone H4	-	?
2.3.1.48	acetyl-CoA + histone H4	acetylation at Lys16	Drosophila melanogaster	CoA + acetylhistone H4	-	?
2.3.1.48	acetyl-CoA + histone H4	acetylation at Lys16	Mus musculus	CoA + acetylhistone H4	-	?
2.3.1.48	additional information	a homologue of Moz, zMoz, occurs in zebrafish to perform a potential Moz function in the trunk region	Danio rerio	?	-	?
2.3.1.48	additional information	HBO1 occurs as a component of a multiprotein complex with histone H3 and H4 acetyltransferase activity in 293 cells. The mammalian complex corresponding to the yeast NuA4 complex contains the MYST HAT Tip60	Homo sapiens	?	-	?
2.3.1.48	additional information	HBO1, Sas2 and Sas3 are involved in transcriptional repression enhancing Sir1-mediated epigenetic gene silencing. NuA3 and NuA4 complexes contain the MYST HATs Sas3 and Esa1, respectively. Sas2 histone acetylation of H4K16 opposed by Sir2 deacetylation of H4K16 at the euchromatin/heterochromatin interface maintains the boundary between regions of transcriptionally active and silent telomeric chromatin. Esa1 plays a role in maintaining the integrity of the DNA, rather than open chromatin structure and high-level transcriptional activity	Saccharomyces cerevisiae	?	-	?
2.3.1.48	additional information	the mammalian complex corresponding to the yeast NuA4 complex contains the MYST HAT Tip60. Myc recruits the Tip60 complex to the chromatin in Rat1 wild-type cells, but not in Rat1 Myc mutant cells. Hbo1 appears to function predominantly in transcriptional repression	Mus musculus	?	-	?
2.3.1.48	additional information	Tip60, in complex with homologues of the mammalian Tip60 complex, exhibits functional redundancy with two other groups of genes, known as synthetic multivulva A and B genes, synMUV. Therefore, the genes encoding proteins of the Tip60 complex are termed class C synMUV genes. SynMUV A and B counteract EGF to Ras to MAPK signaling and the Tip60 complex is a chromatin-modifying complex	Caenorhabditis elegans	?	-	?
2.3.1.48	additional information	a homologue of Moz, zMoz, occurs in zebrafish to perform a potential Moz function in the trunk region	Danio rerio zMoz	?	-	?

Synonyms

EC Number	Synonyms	Comment	Organism
2.3.1.48	chameau	-	Drosophila melanogaster
2.3.1.48	Enok	-	Drosophila melanogaster
2.3.1.48	Esa1	-	Saccharomyces cerevisiae
2.3.1.48	HAM1	-	Arabidopsis thaliana
2.3.1.48	HAM2	-	Arabidopsis thaliana
2.3.1.48	HAT	-	Drosophila melanogaster
2.3.1.48	HAT	-	Mus musculus
2.3.1.48	HAT	-	Homo sapiens
2.3.1.48	HAT	-	Saccharomyces cerevisiae
2.3.1.48	HAT	-	Arabidopsis thaliana
2.3.1.48	HAT	-	Caenorhabditis elegans
2.3.1.48	HAT	-	Danio rerio
2.3.1.48	HBO1	-	Homo sapiens
2.3.1.48	Mof	-	Drosophila melanogaster
2.3.1.48	Mof	-	Mus musculus
2.3.1.48	More	the enzyme belongs to the MYST family histone acetyltransferases which is divided in three sub-families, overview	Drosophila melanogaster
2.3.1.48	More	the enzyme belongs to the MYST family histone acetyltransferases which is divided in three sub-families, overview	Mus musculus
2.3.1.48	More	the enzyme belongs to the MYST family histone acetyltransferases which is divided in three sub-families, overview	Homo sapiens
2.3.1.48	More	the enzyme belongs to the MYST family histone acetyltransferases which is divided in three sub-families, overview	Saccharomyces cerevisiae
2.3.1.48	More	the enzyme belongs to the MYST family histone acetyltransferases which is divided in three sub-families, overview	Arabidopsis thaliana
2.3.1.48	More	the enzyme belongs to the MYST family histone acetyltransferases which is divided in three sub-families, overview	Caenorhabditis elegans
2.3.1.48	More	the enzyme belongs to the MYST family histone acetyltransferases which is divided in three sub-families, overview	Danio rerio
2.3.1.48	Morf	-	Mus musculus
2.3.1.48	Moz related factor	-	Mus musculus
2.3.1.48	Qkf	-	Mus musculus
2.3.1.48	Sas2	-	Saccharomyces cerevisiae
2.3.1.48	Sas3	-	Saccharomyces cerevisiae
2.3.1.48	Tat interacting protein of 60 kDa	-	Mus musculus
2.3.1.48	Tip60	-	Drosophila melanogaster
2.3.1.48	Tip60	-	Mus musculus
2.3.1.48	Tip60	-	Homo sapiens
2.3.1.48	Tip60	-	Caenorhabditis elegans
2.3.1.48	zMoz	-	Danio rerio

Cofactor

EC Number	Cofactor	Comment	Organism
2.3.1.48	acetyl-CoA	-	Drosophila melanogaster
2.3.1.48	acetyl-CoA	-	Mus musculus
2.3.1.48	acetyl-CoA	-	Homo sapiens
2.3.1.48	acetyl-CoA	-	Saccharomyces cerevisiae

General Information

EC Number	General Information	Comment	Organism
2.3.1.48	malfunction	H4K16 hyperacetylation is associated with hyperexpression of the single male X chromosome in flies and, contrasting accordingly, the inactivated X chromosome in human cells is hypoacetylated at the same histone residue. HBO1 appears to function predominantly in transcriptional repression	Homo sapiens
2.3.1.48	physiological function	genome-wide increase in histone acetylation stimulates replication independently of transcription in follicle cells. Enok is essential for mushroom body development, the mushroom bodies are the sites of olfactory learning and memory and in this function equivalent to the mammalian brain. Mof is required for sex chromosome dosage compensation acting in the MSL complex	Drosophila melanogaster
2.3.1.48	physiological function	Qkf/Morf requirement in neural stem cell/neural progenitor self-renewal with an additional role in some other cell types such as osteoblasts and germ cells. Qkf in adult neurogenesis in vivo, overview	Mus musculus
2.3.1.48	physiological function	Sas2 is required for subtelomeric reporter transgene silencing, but also for transcriptional activity of transgenes integrated into rDNA, for transcriptional activation of a mutated HMRE silent mating type locus and for protection of euchromatin from heterochromatin spreading	Saccharomyces cerevisiae