A Noncanonical Bromodomain in the AAA ATPase Protein Yta7 Directs Chromosomal Positioning and Barrier Chromatin Activity

University of Arkansas for Medical Sciences, Department of Biochemistry and Molecular Biology, Little Rock, Arkansas 72205, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 08/2009; 29(17):4604-11. DOI: 10.1128/MCB.00160-09
Source: PubMed


Saccharomyces cerevisiae Yta7 is a barrier active protein that modulates transcriptional states at the silent mating locus, HMR. Additionally, Yta7 regulates histone gene transcription and has overlapping functions with known histone chaperones. This
study focused on deciphering the functional role of the noncanonical Yta7 bromodomain. By use of genetic and epistasis analyses,
the Yta7 bromodomain was shown to be necessary for barrier activity at HMR and to have overlapping functions with histone regulators (Asf1 and Spt16). Canonical bromodomains can bind to acetylated
lysines on histones; however, the Yta7 bromodomain showed an association with histones that was independent of posttranslational
modification. Further investigation showed that regions of Yta7 other than the bromodomain conferred histone association.
Chromatin immunoprecipitation-chip analyses revealed that the Yta7 bromodomain was not solely responsible for histone association
but was also necessary for proper chromosomal positioning of Yta7. This work demonstrates that the Yta7 bromodomain engages
histones for certain cellular functions like barrier chromatin maintenance and particular Spt16/Asf1 cellular pathways of
chromatin regulation.

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Available from: Lauren Blair, Mar 17, 2014
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    • "Yta7 exhibits both physical and genetic interactions with ATP-independent histone chaperones and also core histones. The Yta7 bromodomain interacts with histone tails in an acetylation-independent manner [16], and the N-terminal domain also exhibits an affinity for histones in vitro, indicating the presence of a second chromatin binding region [16]. Deletion of YTA7 results in histone over-accumulation and increased nucleosome density within transcribed sequences [19,20]. "
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    ABSTRACT: Maintenance of the correct level and organisation of nucleosomes is crucial for genome function. Here, we uncover a role for a conserved bromodomain AAA-ATPase, Abo1, in the maintenance of nucleosome architecture in fission yeast. Cells lacking abo1(+) experience both a reduction and mis-positioning of nucleosomes at transcribed sequences in addition to increased intragenic transcription, phenotypes that are hallmarks of defective chromatin re-establishment behind RNA polymerase II. Abo1 is recruited to gene sequences and associates with histone H3 and the histone chaperone FACT. Furthermore, the distribution of Abo1 on chromatin is disturbed by impaired FACT function. The role of Abo1 extends to some promoters and also to silent heterochromatin. Abo1 is recruited to pericentromeric heterochromatin independently of the HP1 ortholog, Swi6, where it enforces proper nucleosome occupancy. Consequently, loss of Abo1 alleviates silencing and causes elevated chromosome mis-segregation. We suggest that Abo1 provides a histone chaperone function that maintains nucleosome architecture genome-wide.
    Full-text · Article · Nov 2015 · EMBO Reports
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    • "However, Gradolatto et al. (2008) identified Yta7 as a repressor of the histone genes, and so there is some disagreement here. Yta7 is a putative ATP-dependent remodeling protein containing a bromodomain that binds preferentially to the tail domain of H3 (Gradolatto et al. 2009). However, Yta7 has little effect on histone mRNA levels , and its activities are not confined to the histone genes: it has direct effects on many inducible genes (Lombardi et al. 2011). "
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    ABSTRACT: We discuss the regulation of the histone genes of the budding yeast Saccharomyces cerevisiae. These include genes encoding the major core histones (H3, H4, H2A, and H2B), histone H1 (HHO1), H2AZ (HTZ1), and centromeric H3 (CSE4). Histone production is regulated during the cell cycle because the cell must replicate both its DNA during S phase and its chromatin. Consequently, the histone genes are activated in late G1 to provide sufficient core histones to assemble the replicated genome into chromatin. The major core histone genes are subject to both positive and negative regulation. The primary control system is positive, mediated by the histone gene-specific transcription activator, Spt10, through the histone upstream activating sequences (UAS) elements, with help from the major G1/S-phase activators, SBF (Swi4 cell cycle box binding factor) and perhaps MBF (MluI cell cycle box binding factor). Spt10 binds specifically to the histone UAS elements and contains a putative histone acetyltransferase domain. The negative system involves negative regulatory elements in the histone promoters, the RSC chromatin-remodeling complex, various histone chaperones [the histone regulatory (HIR) complex, Asf1, and Rtt106], and putative sequence-specific factors. The SWI/SNF chromatin-remodeling complex links the positive and negative systems. We propose that the negative system is a damping system that modulates the amount of transcription activated by Spt10 and SBF. We hypothesize that the negative system mediates negative feedback on the histone genes by histone proteins through the level of saturation of histone chaperones with histone. Thus, the negative system could communicate the degree of nucleosome assembly during DNA replication and the need to shut down the activating system under replication-stress conditions. We also discuss post-transcriptional regulation and dosage compensation of the histone genes.
    Full-text · Article · May 2012 · Genetics
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    • "The noncanonical bromodomain of Yta7 is involved in histone binding, but unlike other bromodomains, binding occurs independently of lysine acetylation (Gradolatto et al. 2009). Elimination of the bromodomain does not completely abolish histone binding; instead, the region of Yta7 with highest affinity for histones lies in its N terminus, which contains the AAA-ATPase domain (Gradolatto et al. 2009). To date, no link between AAA- ATPase function and histone binding has been established. "
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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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