Directional telomeric silencing and lack of canonical B1 elements in two silencer Autonomously Replicating Sequences in S. cerevisiae

BMC Molecular Biology

Krassimir Yankulov²  Kristina Shostak²  Samantha Peeters¹  Patricia Chisamore-Robert² 

[1] Current address: Department of Medical Genetics, Molecular Epigenetics Group, University of British Columbia, Vancouver, Canada;Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada

关键词: Gene silencing;    DNA replication;    Telomere position effect;    Autonomously replicating sequences;   

Others  :  1091402
DOI  :  10.1186/1471-2199-13-34

 received in 2012-09-11, accepted in 2012-11-15,  发布年份 2012

【 摘 要 】

Background

Autonomously Replicating Sequences (ARS) in S. cerevisiae serve as origins of DNA replication or as components of cis-acting silencers, which impose positional repression at the mating type loci and at the telomeres. Both types of ARS can act as replicators or silencers, however it is not clear how these quite diverse functions are executed. It is believed that all ARS contain a core module of an essential ARS Consensus Sequence (ACS) and a non-essential B1 element.

Results

We have tested how the B1 elements contribute to the silencer and replicator function of ARS. We report that the ACS-B1 orientation of ARS has a profound effect on the levels of gene silencing at telomeres. We also report that the destruction of the canonical B1 elements in two silencer ARS (ARS317 and ARS319) has no effect on their silencer and replicator activity.

Conclusions

The observed orientation effects on gene silencing suggest that ARSs can act as both proto-silencers and as insulator elements. In addition, the lack of B1 suggests that the ACS-B1 module could be different in silencer and replicator ARS.

【 授权许可】

   
2012 Chisamore-Robert et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Rusche LN, Kirchmaier AL, Rine J: The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annu Rev Biochem 2003, 72:481-516.
• [2]Marahrens Y, Stillman B: A yeast chromosomal origin of DNA replication defined by multiple functional elements. Science 1992, 255(5046):817-823.
• [3]Rao H, Marahrens Y, Stillman B: Functional conservation of multiple elements in yeast chromosomal replicators. Mol Cell Biol 1994, 14(11):7643-7651.
• [4]Rehman MA, Wang D, Fourel G, Gilson E, Yankulov K: Subtelomeric ACS-containing proto-silencers act as antisilencers in replication factors mutants in Saccharomyces cerevisiae. Mol Biol Cell 2009, 20(2):631-641.
• [5]Lee DG, Bell SP: Architecture of the yeast origin recognition complex bound to origins of DNA replication. Mol Cell Biol 1997, 17(12):7159-7168.
• [6]Rao H, Stillman B: The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators. Proc Natl Acad Sci USA 1995, 92(6):2224-2228.
• [7]Theis JF, Newlon CS: The ARS309 chromosomal replicator of Saccharomyces cerevisiae depends on an exceptional ARS consensus sequence. Proc Natl Acad Sci USA 1997, 94(20):10786-10791.
• [8]Chang F, Theis JF, Miller J, Nieduszynski CA, Newlon CS, Weinreich M: Analysis of chromosome III replicators reveals an unusual structure for the ARS318 silencer origin and a conserved WTW sequence within the origin recognition complex binding site. Mol Cell Biol 2008, 28(16):5071-5081.
• [9]Wilmes GM, Bell SP: The B2 element of the Saccharomyces cerevisiae ARS1 origin of replication requires specific sequences to facilitate pre-RC formation. Proc Natl Acad Sci USA 2002, 99(1):101-106.
• [10]Zou L, Stillman B: Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase. Mol Cell Biol 2000, 20(9):3086-3096.
• [11]Theis JF, Newlon CS: Domain B of ARS307 contains two functional elements and contributes to chromosomal replication origin function. Mol Cell Biol 1994, 14(11):7652-7659.
• [12]Palacios DeBeer MA, Muller U, Fox CA: Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin. Genes Dev 2003, 17(15):1817-1822.
• [13]Chang F, May CD, Hoggard T, Miller J, Fox CA, Weinreich M: High-resolution analysis of four efficient yeast replication origins reveals new insights into the ORC and putative MCM binding elements. Nucleic Acids Res 2011, 39(15):6523-6535.
• [14]Weinreich M, Liang C, Chen HH, Stillman B: Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle. Proc Natl Acad Sci USA 2001, 98(20):11211-11217.
• [15]Zou Y, Yu Q, Bi X: Asymmetric positioning of nucleosomes and directional establishment of transcriptionally silent chromatin by Saccharomyces cerevisiae silencers. Mol Cell Biol 2006, 26(20):7806-7819.
• [16]Zou Y, Yu Q, Chiu YH, Bi X: Position effect on the directionality of silencer function in Saccharomyces cerevisiae. Genetics 2006, 174(1):203-213.
• [17]Bi X, Braunstein M, Shei GJ, Broach JR: The yeast HML I silencer defines a heterochromatin domain boundary by directional establishment of silencing. Proc Natl Acad Sci USA 1999, 96(21):11934-11939.
• [18]Walmsley RW, Chan CS, Tye BK, Petes TD: Unusual DNA sequences associated with the ends of yeast chromosomes. Nature 1984, 310(5973):157-160.
• [19]Chan CS, Tye BK: Organization of DNA sequences and replication origins at yeast telomeres. Cell 1983, 33(2):563-573.
• [20]Fourel G, Lebrun E, Gilson E: Protosilencers as building blocks for heterochromatin. Bioessays 2002, 24(9):828-835.
• [21]Rehman MA, Yankulov K: The dual role of autonomously replicating sequences as origins of replication and as silencers. Curr Genet 2009, 55(4):357-363.
• [22]Tye BK: Minichromosome maintenance as a genetic assay for defects in DNA replication. Methods 1999, 18(3):329-334.
• [23]Yankulov K: Dare to challenge the silence? Telomeric gene silencing revisited. Nucleus 2011, 2(6):513-516.
• [24]Ottaviani A, Gilson E, Magdinier F: Telomeric position effect: from the yeast paradigm to human pathologies? Biochimie 2008, 90(1):93-107.
• [25]Rusche LN, Kirchmaier AL, Rine J: Ordered nucleation and spreading of silenced chromatin in Saccharomyces cerevisiae. Mol Biol Cell 2002, 13(7):2207-2222.
• [26]Kramer DJ, Gauthier L, Yankulov K: Higher-accuracy method for measuring minichromosome stability in Saccharomyces cerevisiae. Biotechniques 2002, 32(5):1036-1040.
• [27]Gottschling DE, Aparicio OM, Billington BL, Zakian VA: Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 1990, 63(4):751-762.
• [28]Fourel G, Revardel E, Koering CE, Gilson E: Cohabitation of insulators and silencing elements in yeast subtelomeric regions. EMBO J 1999, 18(9):2522-2537.
• [29]Huang RY, Kowalski D: Multiple DNA elements in ARS305 determine replication origin activity in a yeast chromosome. Nucleic Acids Res 1996, 24(5):816-823.
• [30]Stillman B: Origin recognition and the chromosome cycle. FEBS Lett 2005, 579(4):877-884.
• [31]Weinreich M, Palacios DeBeer MA, Fox CA: The activities of eukaryotic replication origins in chromatin. Biochim Biophys Acta 2004, 1677(1–3):142-157.
• [32]Lipford JR, Bell SP: Nucleosomes positioned by ORC facilitate the initiation of DNA replication. Mol Cell 2001, 7(1):21-30.
• [33]Murrell A: Setting up and maintaining differential insulators and boundaries for genomic imprinting. Biochem Cell Biol 2011, 89(5):469-478.