Estimating the Prevalence and Regulatory Potential of the Telomere Looping Effect in Yeast Transcription Regulation

Telomeres have long been implicated to have a functional role in the regulation of gene expression. Recent studies have reported that the looping back of telomeres or the telomere looping effect (TLE) can juxtapose genes and regulatory sequences separated by large distances on the same chromosome and facilitate long-distance control of gene expression. In this work we report a detailed investigation on the prevalence and regulatory potential of TLE on a genomic scale by assembling data on protein-DNA interactions from several large-scale ChIp-chip experiments in Saccharomyces cerevisiae. Analysis of the assembled data revealed that a statistically significant number of DNA segments that were inferred to interact with ten or more different transcription factors physically mapped to the ends (telomeric/sub-telomeric regions) from several chromosomes (19 of 32 chromosome ends). For the 83 transcription factors that were inferred to be cross-linked to these DNA segments, we found a statistically significant skew in the distribution of their inferred internal binding sites over the length of the chromosome, such that more than expected binding events occurred proximal to chromosomal ends than elsewhere. These observations suggest the telomere looping effect to be their most likely explanation and imply that a major fraction of the internally bound yeast transcription factors potentially interact with looped back telomeres. Further, we also identified several evolutionarily conserved components of the basal transcriptional machinery that are also frequently linked to these chromosome end segments, strengthening the proposal for a direct interaction between the chromosome ends and internally located transcriptional complexes. We also identified certain chromatin factors that might participate in the TLE and potentially modulate gene expression by chromatin modifications such as histone deacetylation. Our findings provide the first computational evidence for a significant role of long-range regulatory interactions due to telomere looping. These observations also suggest that genome-wide chromatin immunoprecipitation data could be used to systematically uncover regulatory effects of long-range chromatin.

[1]  P. Bork,et al.  Proteome survey reveals modularity of the yeast cell machinery , 2006, Nature.

[2]  Jean-Luc Souciet,et al.  An evolutionary scenario for one of the largest yeast gene families. , 2006, Trends in genetics : TIG.

[3]  A. Dean.  On a chromosome far, far away: LCRs and gene expression. , 2006, Trends in genetics : TIG.

[4]  H. Scherthan,et al.  Set1- and Clb5-deficiencies disclose the differential regulation of centromere and telomere dynamics in Saccharomyces cerevisiae meiosis , 2005, Journal of Cell Science.

[5]  Tony Kouzarides,et al.  Reversing histone methylation , 2005, Nature.

[6]  C. Gustafsson,et al.  The yeast Mediator complex and its regulation. , 2005, Trends in biochemical sciences.

[7]  B. Andrews,et al.  Reverse recruitment: the Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Ingrid Lafontaine,et al.  Comparative genomics in hemiascomycete yeasts: evolution of sex, silencing, and subtelomeres. , 2005, Molecular biology and evolution.

[9]  Y. Zhao,et al.  Central role of Ifh1p–Fhl1p interaction in the synthesis of yeast ribosomal proteins , 2005, The EMBO journal.

[10]  Shoshana J. Wodak,et al.  CYGD: the Comprehensive Yeast Genome Database , 2004, Nucleic Acids Res..

[11]  Job Dekker,et al.  The three 'C' s of chromosome conformation capture: controls, controls, controls , 2005, Nature Methods.

[12]  M. Hall,et al.  TOR Regulates Ribosomal Protein Gene Expression via PKA and the Forkhead Transcription Factor FHL1 , 2004, Cell.

[13]  D. Shore,et al.  Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1 , 2004, Nature.

[14]  K. Struhl,et al.  The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes , 2004, Nature.

[15]  M. Tyers,et al.  A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. , 2004, Genes & development.

[16]  M. Gerstein,et al.  Genomic analysis of regulatory network dynamics reveals large topological changes , 2004, Nature.

[17]  Nicola J. Rinaldi,et al.  Transcriptional regulatory code of a eukaryotic genome , 2004, Nature.

[18]  L. Harper,et al.  A bouquet of chromosomes , 2004, Journal of Cell Science.

[19]  L. Guarente,et al.  The Sir2 family of protein deacetylases. , 2004, Annual review of biochemistry.

[20]  Wendy A Bickmore,et al.  Does looping and clustering in the nucleus regulate gene expression? , 2004, Current opinion in cell biology.

[21]  M. Gerstein,et al.  Structure and evolution of transcriptional regulatory networks. , 2004, Current opinion in structural biology.

[22]  S. Teichmann,et al.  Gene regulatory network growth by duplication , 2004, Nature Genetics.

[23]  Detlef D. Leipe,et al.  Evolutionary history and higher order classification of AAA+ ATPases. , 2004, Journal of structural biology.

[24]  S. Gasser,et al.  Multiple pathways for telomere tethering: functional implications of subnuclear position for heterochromatin formation. , 2004, Biochimica et biophysica acta.

[25]  Cheng-Fu Chang,et al.  Calculating the statistical significance of physical clusters of co-regulated genes in the genome: the role of chromatin in domain-wide gene regulation. , 2004, Nucleic acids research.

[26]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[27]  F. Hediger,et al.  The function of telomere clustering in yeast: the circe effect. , 2004, Cold Spring Harbor symposia on quantitative biology.

[28]  P. Cook.  Nongenic transcription, gene regulation and action at a distance , 2003, Journal of Cell Science.

[29]  H. Bass.  Telomere dynamics unique to meiotic prophase: formation and significance of the bouquet , 2003, Cellular and Molecular Life Sciences CMLS.

[30]  F. Ishikawa,et al.  Composition and conservation of the telomeric complex , 2003, Cellular and Molecular Life Sciences CMLS.

[31]  R. Strich,et al.  Ask10p Mediates the Oxidative Stress-Induced Destruction of the Saccharomyces cerevisiae C-Type Cyclin Ume3p/Srb11p , 2003, Eukaryotic Cell.

[32]  E. Eichler,et al.  Structural Dynamics of Eukaryotic Chromosome Evolution , 2003, Science.

[33]  J. Dekker.  A closer look at long-range chromosomal interactions. , 2003, Trends in biochemical sciences.

[34]  M. Tyers,et al.  The GRID: The General Repository for Interaction Datasets , 2003, Genome Biology.

[35]  M. Gerstein,et al.  Complex transcriptional circuitry at the G1/S transition in Saccharomyces cerevisiae. , 2002, Genes & development.

[36]  Cameron S. Osborne,et al.  Long-range chromatin regulatory interactions in vivo , 2002, Nature Genetics.

[37]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[38]  Craig L. Peterson,et al.  Chromatin Higher Order Folding--Wrapping up Transcription , 2002, Science.

[39]  Mark Ptashne,et al.  Telomere Looping Permits Repression “at a Distance” in Yeast , 2002, Current Biology.

[40]  P. Bourgine,et al.  Topological and causal structure of the yeast transcriptional regulatory network , 2002, Nature Genetics.

[41]  Richard A Young,et al.  Deciphering gene expression regulatory networks. , 2002, Current opinion in genetics & development.

[42]  Heather C. Mefford,et al.  The complex structure and dynamic evolution of human subtelomeres , 2002, Nature Reviews Genetics.

[43]  W. Tham,et al.  Transcriptional silencing at Saccharomyces telomeres: implications for other organisms , 2002, Oncogene.

[44]  Gary D Bader,et al.  Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry , 2002, Nature.

[45]  P. Bork,et al.  Functional organization of the yeast proteome by systematic analysis of protein complexes , 2002, Nature.

[46]  C. Peterson,et al.  Molecular biology. Chromatin higher order folding--wrapping up transcription. , 2002, Science.

[47]  E. Blackburn.  Switching and Signaling at the Telomere , 2001, Cell.

[48]  E. Koonin,et al.  Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system. , 2001, Genome research.

[49]  Harry Scherthan,et al.  A bouquet makes ends meet , 2001, Nature Reviews Molecular Cell Biology.

[50]  E. Koonin,et al.  Cloning the human and mouse MMS19 genes and functional complementation of a yeast mms19 deletion mutant. , 2001, Nucleic acids research.

[51]  S. J. Deminoff,et al.  Rap1p requires Gcr1p and Gcr2p homodimers to activate ribosomal protein and glycolytic genes, respectively. , 2001, Genetics.

[52]  D. Botstein,et al.  Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF , 2001, Nature.

[53]  Mark Ptashne,et al.  Telomere looping permits gene activation by a downstream UAS in yeast , 2001, Nature.

[54]  D. de Bruin,et al.  Telomere Folding Is Required for the Stable Maintenance of Telomere Position Effects in Yeast , 2000, Molecular and Cellular Biology.

[55]  Yudong D. He,et al.  Functional Discovery via a Compendium of Expression Profiles , 2000, Cell.

[56]  T. Lange,et al.  Identification of Human Rap1 Implications for Telomere Evolution , 2000, Cell.

[57]  Qiliang Li,et al.  Locus control regions: coming of age at a decade plus. , 1999, Trends in genetics : TIG.

[58]  L. Bisson,et al.  Transcription of the HXT4 gene is regulated by Gcr1p and Gcr2p in the yeast S. cerevisiae , 1999, Yeast.

[59]  E V Koonin,et al.  AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. , 1999, Genome research.

[60]  P. Grant,et al.  Transcriptional activators direct histone acetyltransferase complexes to nucleosomes , 1998, Nature.

[61]  T. Bestor,et al.  Gene silencing: Methylation meets acetylation , 1998, Nature.

[62]  R. Jessberger,et al.  Chromosome dynamics: the SMC protein family. , 1998, Current opinion in genetics & development.

[63]  D. Shore.  Telomerase and telomere-binding proteins: controlling the endgame. , 1997, Trends in biochemical sciences.

[64]  M. Grunstein.  Molecular model for telomeric heterochromatin in yeast. , 1997, Current opinion in cell biology.

[65]  T. Tsukiyama,et al.  Chromatin remodeling and transcription. , 1997, Current opinion in genetics & development.

[66]  D. Rhodes,et al.  Recognition of telomeric DNA. , 1997, Trends in biochemical sciences.

[67]  A. Wolffe.  Transcriptional control. Sinful repression. , 1997, Nature.

[68]  K. Struhl,et al.  The histone deacetylase RPD3 counteracts genomic silencing in Drosophila and yeast , 1996, Nature.

[69]  L. Pillus,et al.  Activation of an MAP kinase cascade leads to Sir3p hyperphosphorylation and strengthens transcriptional silencing , 1996, The Journal of cell biology.

[70]  V A Zakian,et al.  Telomeres: Beginning to Understand the End , 1995, Science.

[71]  Terrance G. Cooper,et al.  Complilation and characteristics of dedicated transcription factors in Saccharomyces cerevisiae , 1995 .

[72]  Peter Fraser,et al.  Transcription complex stability and chromatin dynamics in vivo , 1995, Nature.

[73]  P. Thuriaux,et al.  The IFH1 gene product interacts with a fork head protein in Saccharomyces cerevisiae , 1995, Yeast.

[74]  D. Shore,et al.  Action of a RAP1 carboxy-terminal silencing domain reveals an underlying competition between HMR and telomeres in yeast. , 1995, Genes & development.

[75]  T. Cooper,et al.  Review: compilation and characteristics of dedicated transcription factors in Saccharomyces cerevisiae. , 1995, Yeast.

[76]  K. Struhl,et al.  Yeast transcriptional regulatory mechanisms. , 1995, Annual review of genetics.

[77]  E. Winter,et al.  DNA binding properties of the Saccharomyces cerevisiae DAT1 gene product. , 1995, Nucleic acids research.

[78]  E. Blackburn.  Telomeres: No end in sight , 1994, Cell.

[79]  A. Lustig,et al.  RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. , 1993, Genes & development.

[80]  Sanjay K. Chhablani,et al.  Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage. , 1993, Genes & development.

[81]  V. Zakian,et al.  Telomeric position effect in yeast. , 1992, Trends in cell biology.

[82]  J S Wall,et al.  DNA looping and Sp1 multimer links: a mechanism for transcriptional synergism and enhancement. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[83]  H. Uemura,et al.  gcr2, a new mutation affecting glycolytic gene expression in Saccharomyces cerevisiae , 1990, Molecular and cellular biology.

[84]  Barbara L. Billington,et al.  Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription , 1990, Cell.

[85]  R. Devlin,et al.  The organization and expression of the light gene, a heterochromatic gene of Drosophila melanogaster. , 1990, Genetics.

[86]  V A Zakian,et al.  Structure and function of telomeres. , 1989, Annual review of genetics.

[87]  G. Kollias,et al.  Position-independent, high-level expression of the human β-globin gene in transgenic mice , 1987, Cell.

[88]  D. Tuan,et al.  The "beta-like-globin" gene domain in human erythroid cells. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[89]  D. Prescott,et al.  All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3' terminus. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[90]  E. Blackburn,et al.  A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. , 1978, Journal of molecular biology.

[91]  Andreas Trumpp,et al.  Chromosome Dynamics in the Yeast Interphase Nucleus , 2022 .