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140

22462537

In which proteins is the chromodomain present?

Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome. CHARGE (coloboma of the eye, heart defects, choanal atresia, retarded growth and development, genital hypoplasia and ear anomalies and/or hearing loss) syndrome is a rare genetic, multiple-malformation syndrome. About 80% of patients with a clinical diagnose, have a mutation or a deletion in the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7). Genotype-phenotype correlation is only partly known. In this nationwide study, phenotypic characteristics of 18 Danish CHD7 mutation positive CHARGE individuals (N = 18) are presented. We studied patient records, clinical photographs, computed tomography, and magnetic resonance imaging (MRI). Information was not available for all traits in all subjects. Therefore, the results are presented as fractions. The following prevalence of cardinal symptoms were found: coloboma, 16/17; heart defects, 14/18; choanal atresia, 7/17; retarded growth and development, 11/13; genital abnormalities, 5/18; ear anomalies, 15/17 and sensorineural hearing loss, 14/15. Vestibular dysfunction (10/13) and swallowing problems (12/15) were other frequent cranial nerve dysfunctions. Three-dimensional reconstructions of MRI scans showed temporal bone abnormalities in >85%. CHARGE syndrome present a broad phenotypic spectrum, although some clinical features are more frequently occurring than others. Here, we suggest that genetic testing for CHD7 mutation should be considered in neonates with a specific combination of several clinical symptoms.

140

23020525

In which proteins is the chromodomain present?

CHD1L protein is overexpressed in human ovarian carcinomas and is a novel predictive biomarker for patients survival. BACKGROUND: Our recent studies suggested that the chromodomain helicase DNA binding protein 1-like (CHD1L) gene plays an oncogenic role in human hepatocellular carcinoma. However, the status of CHD1L protein expression in ovarian cancer and its clinical/prognostic significance are obscure. METHODS: In this study, immunohistochemistry (IHC) for CHD1L was performed on a tissue microarray (TMA) containing 102 primary ovarian carcinomas and 44 metastatic lesions (omental metastasis). Receiver-operator curve (ROC) analysis was used to evaluate patients' survival status. RESULTS: There is an augmented tendency of CHD1L expression in ovarian carcinoma metastasis than in primary lesions (P<0.05). A significant association was found between positive expression of CHD1L and tumors histological type (P <0.05). By univariate survival analysis of the ovarian carcinoma cohorts, positive expression of CHD1L was significantly correlated with shortened patient survival (mean 66.7 months versus 97.4 months, P<0.05). Moreover, CHD1L expression was evaluated to be a significant and independent prognostic factor in multivariate analysis (P<0.05). CONCLUSIONS: These findings provide evidence that positive expression of CHD1L protein is significantly correlated with the metastasis proceeding of ovarian carcinoma, and CHD1L protein expression, as examined by IHC, may act as a novel prognostic biomarker for patients with ovarian carcinoma.

140

22551706

In which proteins is the chromodomain present?

Enforcing silencing: dynamic HP1 complexes in Neurospora. Analysis of the Neurospora crassa chromodomain protein CDP-2, a component of a newly characterized HP1-containing complex, reveals a second gene-silencing mechanism and provides insights into the dynamic nature of chromatin domains that possess shared components.

140

23403278

In which proteins is the chromodomain present?

Dysregulation of cell cycle control caused by overexpression of the oncogene pp32r1 (ANP32C) and the Tyr>His mutant pp32r1Y140H. The pp32 (ANP32A) gene acts as a tumor suppressor while its closely related homologue pp32r1 (ANP32C) is oncogenic and is overexpressed in breast, prostate and pancreatic tumors. The transduction of p53wt cell lines (ACHN and HeLa) with pp32r1 or pp32r1Y140H lentivirus increased the proliferation of p53wt cell lines compared to the untransduced control cells while transduction of the p53(R248W) MiaPaCa2 cell line had no effect. Cell cycle analysis of transduced ACHN cells by PI staining and BrdU incorporation illustrated a pronounced shift toward the S-phase of the cell cycle in cells overexpressing the pp32r1 and pp32r1Y140H proteins. Confocal microscopy and western blotting demonstrated that pp32r1 and the pp32r1Y140H mutant protein reside predominantly in the cytoplasm in constrast to pp32 which is a nuclear/cytoplasmic shuttling protein. To determine the effects of pp32r1 or pp32r1Y140H overexpression at the proteomic level we performed a comprehensive proteome analysis on ACHN, ACHN-pp32r1 and ACHN-pp32r1Y140H cell lysates using the isotope-coded protein label (ICPL) method. Among those proteins with >40% regulation were Macrophage Capping protein (CAPG) and Chromodomain Helicase DNA binding protein 4 (CHD4) proteins which were significantly upregulated by pp32r1 and pp32r1Y140H overexpression. This increase in CHD4 also appears to influence a number of cell cycle regulator genes including; p53, p21 and cyclinD1 as judged by western blotting. Silencing of CHD4 in ACHN-pp32r1Y140H cells using specific shRNA reverted the cell cycle dysregulation caused by pp32r1Y140H expression to that of the untransduced ACHN cell line, suggesting that CHD4 is the prominent effector of the pp32r1/pp32r1Y140H phenotype.

140

22528993

In which proteins is the chromodomain present?

Cellular alterations and modulation of protein expression in bitumen-challenged human osteoblast cells. PURPOSE: There are many arguments on the carcinogenic potential of bitumen extract. The mechanism of bitumen-induced damage is not well understood at the molecular level. Therefore, in the present study, cell-transforming and tumor-inducing potential of bitumen extract was studied using in vitro [human osteosarcoma (HOS) cells] and in vivo [nude and severe combined immunodeficiency (SCID) mice] models. METHODS: Gas chromatography/mass spectrometry (GC/MS) analysis was carried out to find out the existence of carcinogenic compounds in the bitumen extract. Cell transformation test, anchorage independence assay, karyotyping assay, tumorigenicity assay, and 2-DE analysis were used to find out the effect of bitumen using the in vitro and in vivo models. RESULTS: GC/MS analysis showed the existence of carcinogenic compounds in the bitumen extract. HOS cells were treated with different concentrations (25, 50, and 100 μl/ml) of bitumen extract. Compared to the parental HOS cells, bitumen transformants (HOS T1 and HOS T2) showed the characteristics of anchorage independency, chromosomal anomaly, and cellular transformation. Interestingly, bitumen transformants were not able to form tumor in nude/SCID mice. Proteomic analysis revealed the existence of 19 differentially expressed proteins involved in progression of cancer, angiogenesis, cell adhesion, etc. CONCLUSIONS: Exposure of bitumen extract to HOS cells results in the cellular transformation similar to cancer cells and can modulate proteins involved in the progression of cancer. We state that the non-tumorogenic potential of bitumen transformant in nude/SCID mice can be attributed to the downregulation of galectin-1, chromodomain helicase DNA-binding protein 1-like gene, and membrane-associated guanylate kinase 2 protein.

140

21720545

In which proteins is the chromodomain present?

Structural and histone binding ability characterizations of human PWWP domains. BACKGROUND: The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. METHODOLOGY/PRINCIPAL FINDINGS: The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. CONCLUSIONS: PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical β-barrel core, an insertion motif between the second and third β-strands and a C-terminal α-helix bundle. Both the canonical β-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

140

22186629

In which proteins is the chromodomain present?

CHD5, a tumor suppressor that is epigenetically silenced in lung cancer. Chromodomain helicase DNA binding protein 5 (CHD5) is a potent tumor suppressor that serves as a master regulator of a tumor-suppressive network. Examination of the role played by CHD5 in a wide range of human cancers is warranted. In this study, we focused on the epigenetic modification and tumor-suppressive role of CHD5 in lung cancer. We measured CHD5 mRNA and protein expression in lung cancer cells, lung cancer tissues, and their corresponding noncancerous lung tissues using real-time PCR and Western blot analysis. We then determined the methylation status of the CHD5 promoter in these samples using methylation-specific sequencing and analyzed CHD5 re-expression in lung cancer cells treated with or without 5-aza-2-deoxycytidine, an inhibitor of DNA methylation. Next, the lung cancer cell clones stably expressing EGFP-CHD5 protein or EGFP protein, respectively, were obtained and the effects of restored CHD5 expression on cell proliferation, colony formation, and tumorigenicity were assessed. CHD5 expression ranged from low to absent in the lung cancer cell lines and tissues examined; the CHD5 promoter was hyperethylated in these samples. Treatment with 5-aza-dC resulted in a localized decrease in methylation density and an increase in CHD5 expression. Clonogenicity and tumor growth were abrogated in A549 and H1299 cells upon restoration of CHD5 expression. A significant reduction in clonogenicity was observed; an average of 47.83 ± 4.6% reduction for A549-EGFP-CHD5 was observed compared to A549-EGFP, and an average of 56.39 ± 5.3% reduction for H1299-EGFP-CHD5 was observed compared to H1299-EGFP. A549-EGFP exhibited an average tumor size of 452.3 ± 36.5 mm(3), whereas A549-EGFP-CHD5 exhibited an average tumor size of only 57.7 ± 18.5 mm(3). Thus, our findings indicate that CHD5 is a potential tumor suppressor gene that is inactivated via an epigenetic mechanism in lung cancer.

140

15457214

In which proteins is the chromodomain present?

Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3. Both DNA methylation and post-translational histone modifications contribute to gene silencing, but the mechanistic relationship between these epigenetic marks is unclear. Mutations in two Arabidopsis genes, the KRYPTONITE (KYP) histone H3 lysine 9 (H3K9) methyltransferase and the CHROMOMETHYLASE3 (CMT3) DNA methyltransferase, cause a reduction of CNG DNA methylation, suggesting that H3K9 methylation controls CNG DNA methylation. Here we show that the chromodomain of CMT3 can directly interact with the N-terminal tail of histone H3, but only when it is simultaneously methylated at both the H3K9 and H3K27 positions. Furthermore, using chromatin immunoprecipitation analysis and immunohistolocalization experiments, we found that H3K27 methylation colocalizes with H3K9 methylation at CMT3-controlled loci. The H3K27 methylation present at heterochromatin was not affected by mutations in KYP or in several Arabidopsis PcG related genes including the Enhancer of Zeste homologs, suggesting that a novel pathway controls heterochromatic H3K27 methylation. Our results suggest a model in which H3K9 methylation by KYP, and H3K27 methylation by an unknown enzyme provide a combinatorial histone code for the recruitment of CMT3 to silent loci.

140

16537902

In which proteins is the chromodomain present?

Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. The chromodomain (CD) of the Drosophila Polycomb protein exhibits preferential binding affinity for histone H3 when trimethylated at lysine 27. Here we have investigated the five mouse Polycomb homologs known as Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8. Despite a high degree of conservation, the Cbx chromodomains display significant differences in binding preferences. Not all CDs bind preferentially to K27me3; rather, some display affinity towards both histone H3 trimethylated at K9 and H3K27me3, and one CD prefers K9me3. Cbx7, in particular, displays strong affinity for both H3K9me3 and H3K27me3 and is developmentally regulated in its association with chromatin. Cbx7 associates with facultative heterochromatin and, more specifically, is enriched on the inactive X chromosome. Finally, we find that, in vitro, the chromodomain of Cbx7 can bind RNA and that, in vivo, the interaction of Cbx7 with chromatin, and the inactive X chromosome in particular, depends partly on its association with RNA. We propose that the capacity of this mouse Polycomb homolog to associate with the inactive X chromosome, or any other region of chromatin, depends not only on its chromodomain but also on the combination of histone modifications and RNA molecules present at its target sites.

140

8460153

In which proteins is the chromodomain present?

A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2-like helicase domain. Two overlapping cDNAs that encode a 197-kDa sequence-selective DNA-binding protein were isolated from libraries derived from mouse lymphoid cell mRNA. In addition to a DNA-binding domain, the protein contains both a chromodomain, which occurs in proteins that are implicated in chromatin compaction, and an SNF2/SWI2-like helicase domain, which occurs in proteins that are believed to activate transcription by counteracting the repressive effects of chromatin structure. A Southern blot analysis indicated that this protein, which we have named CHD-1, for chromodomain-helicase-DNA-binding protein, is present in most, if not all, mammalian species. A Northern blot analysis revealed multiple CHD mRNA components that differed both qualitatively and quantitatively among various cell types. The various mRNAs, which are probably produced by alternative RNA processing, could conceivably encode tissue-specific and developmental stage-specific isoforms of the protein. Based on its interesting combination of features, we suspect that CHD-1 plays an important role in gene regulation.

140

18450745

In which proteins is the chromodomain present?

Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs. Previous studies have shown two homologous chromodomain modules in the HP1 and Polycomb proteins exhibit discriminatory binding to related methyllysine residues (embedded in ARKS motifs) of the histone H3 tail. Methylated ARK(S/T) motifs have recently been identified in other chromatin factors (e.g. linker histone H1.4 and lysine methyltransferase G9a). These are thought to function as peripheral docking sites for the HP1 chromodomain. In vertebrates, HP1-like chromodomains are also present in the chromodomain Y chromosome (CDY) family of proteins adjacent to a putative catalytic motif. The human genome encodes three CDY family proteins, CDY, CDYL, and CDYL2. These have putative functions ranging from establishment of histone H4 acetylation during spermiogenesis to regulation of transcription co-repressor complexes. To delineate the biochemical functions of the CDY family chromodomains, we analyzed their specificity of methyllysine recognition. We detected substantial differences among these factors. The CDY chromodomain exhibits discriminatory binding to lysine-methylated ARK(S/T) motifs, whereas the CDYL2 chromodomain binds with comparable strength to multiple ARK(S/T) motifs. Interestingly, subtle amino acid changes in the CDYL chromodomain prohibit such binding interactions in vitro and in vivo. However, point mutations can rescue binding. In support of the in vitro binding properties of the chromodomains, the full-length CDY family proteins exhibit substantial variability in chromatin localization. Our studies underscore the significance of subtle sequence differences in a conserved signaling module for diverse epigenetic regulatory pathways.

140

21224386

In which proteins is the chromodomain present?

Role of Swi6/HP1 self-association-mediated recruitment of Clr4/Suv39 in establishment and maintenance of heterochromatin in fission yeast. Swi6/HP1, an evolutionarily conserved protein, is critical for heterochromatin assembly in fission yeast and higher eukaryotes. In fission yeast, histone deacetylation by histone deacetylases is thought to be followed by H3-Lys-9 methylation by the histone methyltransferase Clr4/Suv39H1. H3-Lys-9-Me2 interacts with the chromodomain of Swi6/HP1. Swi6/HP1 is thought to act downstream of Clr4/Suv39, and further self-association of Swi6/HP1 is assumed to stabilize the heterochromatin structure. Here, we show that the self-association-defective mutant of Swi6 does not interact with Clr4. It not only fails to localize to heterochromatin loci but also interferes with heterochromatic localization of H3-Lys-9-Me2 (and thereby Clr4) and the endogenous Swi6 in a dominant negative manner. Thus, self-association of Swi6/HP1 helps in binding to and recruitment of Clr4 and thereby in establishment and maintenance of heterochromatin by a concerted rather than a sequential mechanism.

140

11500496

In which proteins is the chromodomain present?

MRG15 activates the B-myb promoter through formation of a nuclear complex with the retinoblastoma protein and the novel protein PAM14. The MORF4-Related Gene on chromosome 15 (MRG15) is a member of a novel family of genes originally identified in studies to reveal cell senescence-inducing factors. MRG15 contains several predicted protein motifs, including a nuclear localization signal, a helix-loop-helix region, a leucine zipper, and a chromodomain. These motifs are commonly associated with transcription factors, suggesting that MRG15 may likewise function as a transcriptional regulator. To examine the potential function(s) of MRG15, we sought to identify cellular factors associated with this MRG family member. In this regard, we have found that both the retinoblastoma tumor suppressor (Rb) and a novel nuclear protein PAM14 (Protein Associated with MRG, 14 kDa) specifically associate with MRG15. We have further demonstrated that these interactions require the helix-loop-helix and leucine zipper domains of MRG15. Interestingly we have found all three proteins present in a multiprotein complex, suggesting that at least some of their functions may be interdependent. Although the functions of PAM14 have yet to be elucidated, Rb has several well characterized activities, including repression of E2F-activated promoters such as that of B-myb. Significantly we have demonstrated that MRG15 blocks the Rb-induced repression of this promoter, leading to B-myb promoter activation. Collectively these results suggest that MRG15 regulates transcription through interactions with a cellular protein complex containing Rb and PAM14.

140

22646239

In which proteins is the chromodomain present?

Identification of CHD7S as a novel splicing variant of CHD7 with functions similar and antagonistic to those of the full-length CHD7L. CHD7 is one of the nine members of the chromodomain helicase DNA-binding family of ATP-dependent chromatin remodeling enzymes. Mutations in CHD7 give rise to CHARGE syndrome, a human condition characterized by malformation of various organs. We have now identified a novel transcript of CHD7 that is generated by alternative splicing of exon 6. The protein encoded by this variant transcript (termed CHD7S) lacks one of the two chromodomains as well as the helicase/ATPase domain, DNA-binding domain and BRK domains of the full-length protein (CHD7L). CHD7S was found to localize specifically to the nucleolus in a manner dependent on a nucleolar localization signal. Over-expression of CHD7S, as well as that of CHD7L, resulted in an increase in 45S precursor rRNA production. Conversely, depletion of both CHD7S and CHD7L by RNA interference inhibited both 45S precursor rRNA production and cell proliferation to a greater extent than did depletion of CHD7L alone. Furthermore, we found that, like CHD7L, CHD7S binds to Sox2 in the nucleoplasm. Unexpectedly, however, whereas over-expression of CHD7L promoted Sox2-mediated transcriptional regulation, over-expression of CHD7S suppressed it. These results indicate that CHD7S functions cooperatively or antagonistically with CHD7L in the nucleolus and nucleoplasm, respectively.

140

22715096

In which proteins is the chromodomain present?

Kruppel-associated Box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1β (HP1-β) mobilization and DNA repair in heterochromatin. The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-β, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-β from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-β exchange from heterochromatin, promoting DNA repair.

140

21047797

In which proteins is the chromodomain present?

Recognition and specificity determinants of the human cbx chromodomains. The eight mammalian Cbx proteins are chromodomain-containing proteins involved in regulation of heterochromatin, gene expression, and developmental programs. They are evolutionarily related to the Drosophila HP1 (dHP1) and Pc (dPc) proteins that are key components of chromatin-associated complexes capable of recognizing repressive marks such as trimethylated Lys-9 and Lys-27, respectively, on histone H3. However, the binding specificity and function of the human homologs, Cbx1-8, remain unclear. To this end we employed structural, biophysical, and mutagenic approaches to characterize the molecular determinants of sequence contextual methyllysine binding to human Cbx1-8 proteins. Although all three human HP1 homologs (Cbx1, -3, -5) replicate the structural and binding features of their dHP counterparts, the five Pc homologs (Cbx2, -4, -6, -7, -8) bind with lower affinity to H3K9me3 or H3K27me3 peptides and are unable to distinguish between these two marks. Additionally, peptide permutation arrays revealed a greater sequence tolerance within the Pc family and suggest alternative nonhistone sequences as potential binding targets for this class of chromodomains. Our structures explain the divergence of peptide binding selectivity in the Pc subfamily and highlight previously unrecognized features of the chromodomain that influence binding and specificity.

140

21669865

In which proteins is the chromodomain present?

Synthetic reversal of epigenetic silencing. Controlling cell fate-determining gene expression is key to stem cell differentiation, tissue regeneration, and cancer therapy. To date, custom-built transcription factors recognize the information encoded in specific DNA sequences. Chromatin proteins undergo covalent modifications and form complexes that encode a second layer of information that determines proximal gene activity. Here, we employ a novel gene-targeting approach that exploits a specific chromatin modification to reactivate silenced loci in human cells. We used the human Polycomb chromatin protein and homologues from other species to construct modular synthetic transcription factors, called Pc-TFs, that recognize the repressive trimethyl-histone H3 lysine 27 (H3K27me3) signal and switch silenced genes to an active state. Pc-TF expression in U2OS osteosarcoma cells leads to increased transcription of the senescence locus CDKN2A (p16) and other loci in a chromodomain- and activation module-dependent manner, a switch to a senescence phenotype, and reduced cell proliferation. These results indicate that silenced developmental regulators can be reactivated by a synthetic transcription factor that interacts with chromatin rather than DNA, resulting in an altered cell state. As such, our work extends the flexibility of transcription factor engineering and is the first example of chromatin-mediated synthetic transcription factor targeting.

140

16339723

In which proteins is the chromodomain present?

MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii. The restructuring of chromatin precedes tightly regulated events such as DNA transcription, replication, and repair. One type of chromatin remodeling involves the covalent modification of nucleosomes by histone acetyltransferase (HAT) complexes. The observation that apicidin exerts antiprotozoal activity by targeting a histone deacetyltransferase has prompted our search for more components of the histone modifying machinery in parasitic protozoa. We have previously identified GNAT family HATs in the opportunistic pathogen Toxoplasma gondii and now describe the first MYST (named for members MOZ, Ybf2/Sas3, Sas2, and Tip60) family HATs in apicomplexa (TgMYST-A and -B). The TgMYST-A genomic locus is singular and generates a approximately 3.5-kb transcript that can encode two proteins of 411 or 471 amino acids. TgMYST-B mRNA is approximately 7.0 kb and encodes a second MYST homologue. In addition to the canonical MYST HAT catalytic domain, both TgMYST-A and -B possess an atypical C2HC zinc finger and a chromodomain. Recombinant TgMYST-A exhibits a predilection to acetylate histone H4 in vitro at lysines 5, 8, 12, and 16. Antibody generated to TgMYST-A reveals that both the long and short (predominant) versions are present in the nucleus and are also plentiful in the cytoplasm. Moreover, both TgMYST-A forms are far more abundant in rapidly replicating parasites (tachyzoites) than encysted parasites (bradyzoites). A bioinformatics survey of the Toxoplasma genome reveals numerous homologues known to operate in native MYST complexes. The characterization of TgMYST HATs represents another important step toward understanding the regulation of gene expression in pathogenic protozoa and provides evolutionary insight into how these processes operate in eukaryotic cells in general.