Saccharomyces cerevisiae Yta7 Regulates Histone Gene Expression

Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Genetics (Impact Factor: 5.96). 06/2008; 179(1):291-304. DOI: 10.1534/genetics.107.086520
Source: PubMed


The Saccharomyces cerevisiae Yta7 protein is a component of a nucleosome bound protein complex that maintains distinct transcriptional zones of chromatin. We previously found that one protein copurifying with Yta7 is the yFACT member Spt16. Epistasis analyses revealed a link between Yta7, Spt16, and other previously identified members of the histone regulatory pathway. In concurrence, Yta7 was found to regulate histone gene transcription in a cell-cycle-dependent manner. Association at the histone gene loci appeared to occur through binding of the bromodomain-like region of Yta7 with the N-terminal tail of histone H3. Our work suggests a mechanism in which Yta7 is localized to chromatin to establish regions of transcriptional silencing, and that one facet of this cellular mechanism is to modulate transcription of histone genes.

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Available from: Richard Scott Rogers, Jun 15, 2015
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    • "Our study provides a detailed analysis of regulation of cell cycle-dependent histone gene transcription through phosphorylation of the chromatin boundary element Yta7 by S forms of Cdk1 and CK2. As overexpression of a yta7 phosphomutant is highly toxic and Yta7 localizes also to numerous other loci (Gradolatto et al. 2008), we propose that S-phase-specific regulation of Yta7 by Cdk1 and CK2 may be a mechanism that is broadly applied throughout the genome to regulate gene transcription. Interestingly, the human homolog of Yta7, ATAD2, is involved in chromatin dynamics and transcriptional activities and is up-regulated predominantly in G1/S- phase cells, consistent with a possible role in DNA replication and histone synthesis (Ciro et al. 2009; Caron et al. 2010). "
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    ABSTRACT: The cell cycle-regulated expression of core histone genes is required for DNA replication and proper cell cycle progression in eukaryotic cells. Although some factors involved in histone gene transcription are known, the molecular mechanisms that ensure proper induction of histone gene expression during S phase remain enigmatic. Here we demonstrate that S-phase transcription of the model histone gene HTA1 in yeast is regulated by a novel attach-release mechanism involving phosphorylation of the conserved chromatin boundary protein Yta7 by both cyclin-dependent kinase 1 (Cdk1) and casein kinase 2 (CK2). Outside S phase, integrity of the AAA-ATPase domain is required for Yta7 boundary function, as defined by correct positioning of the histone chaperone Rtt106 and the chromatin remodeling complex RSC. Conversely, in S phase, Yta7 is hyperphosphorylated, causing its release from HTA1 chromatin and productive transcription. Most importantly, abrogation of Yta7 phosphorylation results in constitutive attachment of Yta7 to HTA1 chromatin, preventing efficient transcription post-recruitment of RNA polymerase II (RNAPII). Our study identified the chromatin boundary protein Yta7 as a key regulator that links S-phase kinases with RNAPII function at cell cycle-regulated histone gene promoters.
    Full-text · Article · Dec 2011 · Genes & development
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    • "In humans, ATAD2 is an E2F target gene that binds to the MYC oncogene (Ciró et al. 2009). High ATAD2 levels correlate with a higher risk of distant recurrence in breast cancer, and mutation of the bromodomain in ATAD2 impairs the binding between ATAD2 and histone H3 (Ciró et al. 2009; see also Gradolatto et al. 2008). Additionally, knocking down ATAD2 expression inhibits estrogen-mediated induction of cyclin D1, c-myc and E2F1 mRNA, and mutating the AAA ATPase domain reduces estrogen-mediated induction of cyclin D1 and E2F1 (Zou et al. 2007). "
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    ABSTRACT: ATAD2 is an E2F target gene that is highly expressed in gastrointestinal and breast carcinomas. Here we characterize a related gene product, ATAD2B. Both genes are evolutionarily conserved, with orthologues present in all eukaryotic genomes examined. Human ATAD2B shows a high degree of similarity to ATAD2. Both contain an AAA domain and a bromodomain with amino acid sequences sharing 97% and 74% identity, respectively. The expression of ATAD2B was studied in the chicken embryo using a polyclonal antibody raised against a recombinant fragment of human ATAD2B. Immunohistochemistry revealed transient nuclear expression in subpopulations of developing neurons. The transient nature of the expression was confirmed by immunoblotting homogenates of the developing telencephalon. Cell fractionation was used to confirm the nuclear localization of ATAD2B in the developing nervous system: anti-ATAD2B recognizes a smaller band (approximately 160 kDa) in the nuclear fraction and a larger band (approximately 300 kDa) in the membrane fraction, suggesting that posttranslational processing of ATAD2B may regulate its transport to the nucleus. The expression of ATAD2B was also studied in human tumors. Oncomine and immunohistochemistry reveal ATAD2B expression in glioblastoma and oligodendroglioma; ATAD2B immunostaining was also elevated in human breast carcinoma. In tumors ATAD2B appears to be cytoplasmic or membrane bound, and not nuclear. Our observations suggest that ATAD2B may play a role in neuronal differentiation and tumor progression.
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    • "The analysis of the encoded protein revealed the presence of a bromodomain and an ATPase domain of the AAA family ('ATPases associated with diverse cellular activities') suggesting functions related to genome regulation. Accordingly, work on its yeast ortholog showed its role in the maintenance of boundaries, critical for the functional organization of the genome in Saccaromyces cerevisiae (Jambunathan et al., 2005; Tackett et al., 2005; Fillingham et al., 2009), as well as in the transcriptional regulation of histone genes (Gradolatto et al., 2008). In addition, a genetic screen in Caenorabditis elegans suggests its involvement in the silencing of repeated transgenes (Tseng et al., 2007). "
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    ABSTRACT: Cancer cells frequently express genes normally active in male germ cells. ATAD2 is one of them encoding a conserved factor harbouring an AAA type ATPase domain and a bromodomain. We show here that ATAD2 is highly expressed in testis as well as in many cancers of different origins and that its high expression is a strong predictor of rapid mortality in lung and breast cancers. These observations suggest that ATAD2 acts on upstream and basic cellular processes to enhance oncogenesis in a variety of unrelated cell types. Accordingly, our functional studies show that ATAD2 controls chromatin dynamics, genome transcriptional activities and apoptotic cell response. We could also highlight some of the important intrinsic properties of its two regulatory domains, including a functional cross-talk between the AAA ATPase domain and the bromodomain. Altogether, these data indicate that ATAD2 overexpression in somatic cells, by acting on basic properties of chromatin, may contribute to malignant transformation.
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