Core promoter T-blocks correlate with gene expression levels in C. elegans.

Core promoters mediate transcription initiation by the integration of diverse regulatory signals encoded in the proximal promoter and enhancers. It has been suggested that genes under simple regulation may have low-complexity permissive promoters. For these genes, the core promoter may serve as the principal regulatory element; however, the mechanism by which this occurs is unclear. We report here a periodic poly-thymine motif, which we term T-blocks, enriched in occurrences within core promoter forward strands in Caenorhabditis elegans. An increasing number of T-blocks on either strand is associated with increasing nucleosome eviction. Strikingly, only forward strand T-blocks are correlated with expression levels, whereby genes with ≥6 T-blocks have fivefold higher expression levels than genes with ≤3 T-blocks. We further demonstrate that differences in T-block numbers between strains predictably affect expression levels of orthologs. Highly expressed genes and genes in operons tend to have a large number of T-blocks, as well as the previously characterized SL1 motif involved in trans-splicing. The presence of T-blocks thus correlates with low nucleosome occupancy and the precision of a trans-splicing motif, suggesting its role at both the DNA and RNA levels. Collectively, our results suggest that core promoters may tune gene expression levels through the occurrences of T-blocks, independently of the spatio-temporal regulation mediated by the proximal promoter.

[1]  G. Salina,et al.  Attraction, phasing and neighbour effects of histone octamers on curved DNA. , 1990, Journal of molecular biology.

[2]  A. Prunell Nucleosome reconstitution on plasmid‐inserted poly(dA) . poly(dT). , 1982, The EMBO journal.

[3]  J. Spieth,et al.  Insertion of part of an intron into the 5' untranslated region of a Caenorhabditis elegans gene converts it into a trans-spliced gene , 1991, Molecular and cellular biology.

[4]  D. Cavener,et al.  Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates. , 1987, Nucleic acids research.

[5]  Shigehiko Kanaya,et al.  Periodicity in prokaryotic and eukaryotic genomes identified by power spectrum analysis. , 2002, Gene.

[6]  John T. Lis,et al.  Defining mechanisms that regulate RNA polymerase II transcription in vivo , 2009, Nature.

[7]  B. Pugh,et al.  A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae. , 2004, Molecular cell.

[8]  T. Blumenthal Trans-splicing and operons. , 2005, WormBook : the online review of C. elegans biology.

[9]  Thomas Blumenthal,et al.  Caenorhabditis elegans operons: form and function , 2003, Nature Reviews Genetics.

[10]  Rosa Alcazar,et al.  Unusual DNA Structures Associated With Germline Genetic Activity in Caenorhabditis elegans , 2006, Genetics.

[11]  Steven M. Johnson,et al.  A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. , 2008, Genome research.

[12]  C. Verrijzer,et al.  DNA binding site selection by RNA polymerase II TAFs: a TAFII250–TAFII150 complex recognizes the Initiator , 1999, The EMBO journal.

[13]  D. Baltimore,et al.  The “initiator” as a transcription control element , 1989, Cell.

[14]  W. Gish,et al.  Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map , 2001, Nature Genetics.

[15]  Bing Li,et al.  The Role of Chromatin during Transcription , 2007, Cell.

[16]  J. Vanwye,et al.  Species-specific patterns of DNA bending and sequence. , 1991, Nucleic acids research.

[17]  Junjun Zhang,et al.  BioMart Central Portal—unified access to biological data , 2009, Nucleic Acids Res..

[18]  A. Fire,et al.  Partitioning the C. elegans genome by nucleosome modification, occupancy, and positioning , 2010, Chromosoma.

[19]  Irene K. Moore,et al.  A genomic code for nucleosome positioning , 2006, Nature.

[20]  E. Davidson The Regulatory Genome: Gene Regulatory Networks In Development And Evolution , 2006 .

[21]  A. Fire,et al.  Structural analysis of hyperperiodic DNA from Caenorhabditis elegans , 2006, Nucleic acids research.

[22]  Zhiping Weng,et al.  Analysis of overrepresented motifs in human core promoters reveals dual regulatory roles of YY1. , 2007, Genome research.

[23]  Irene K. Moore,et al.  The DNA-encoded nucleosome organization of a eukaryotic genome , 2009, Nature.

[24]  Michael Gribskov,et al.  Combining evidence using p-values: application to sequence homology searches , 1998, Bioinform..

[25]  S. Carroll Evo-Devo and an Expanding Evolutionary Synthesis: A Genetic Theory of Morphological Evolution , 2008, Cell.

[26]  E. Segal,et al.  Poly(da:dt) Tracts: Major Determinants of Nucleosome Organization This Review Comes from a Themed Issue on Protein-nucleic Acid Interactions Edited , 2022 .

[27]  Michael D. Wilson,et al.  Five-Vertebrate ChIP-seq Reveals the Evolutionary Dynamics of Transcription Factor Binding , 2010, Science.

[28]  Job Harms,et al.  THE LANDSCAPE OF , 2010 .

[29]  Michael Lewis Goldberg,et al.  Sequence analysis of Drosophila histone genes , 1979 .

[30]  Jack D. Griffith,et al.  The terminus of SV40 DNA replication and transcription contains a sharp sequence-directed curve , 1988, Cell.

[31]  J. T. Kadonaga,et al.  Enhancer-promoter specificity mediated by DPE or TATA core promoter motifs. , 2001, Genes & development.

[32]  G. Rubin,et al.  Computational analysis of core promoters in the Drosophila genome , 2002, Genome Biology.

[33]  Matthias E. Futschik,et al.  DNA Motifs and Sequence Periodicities , 2006, Silico Biol..

[34]  T Lagrange,et al.  New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor IIB. , 1998, Genes & development.

[35]  Alexander Stark,et al.  Comparative Genomics of Gene Regulation—conservation and Divergence of Cis-regulatory Information This Review Comes from a Themed Issue on Genomes and Evolution Edited Main Text Conflict of Interest , 2022 .

[36]  J. T. Kadonaga,et al.  Regulation of gene expression via the core promoter and the basal transcriptional machinery. , 2010, Developmental biology.

[37]  Itai Yanai,et al.  Comparison of diverse developmental transcriptomes reveals that coexpression of gene neighbors is not evolutionarily conserved. , 2009, Genome research.

[38]  Karin Kiontke,et al.  The phylogenetic relationships of Caenorhabditis and other rhabditids. , 2005, WormBook : the online review of C. elegans biology.

[39]  T. Burke,et al.  Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters. , 1996, Genes & development.

[40]  Naama Barkai,et al.  The design of transcription-factor binding sites is affected by combinatorial regulation , 2005, Genome Biology.

[41]  Charles Elkan,et al.  Fitting a Mixture Model By Expectation Maximization To Discover Motifs In Biopolymer , 1994, ISMB.

[42]  James T Kadonaga,et al.  Rational design of a super core promoter that enhances gene expression , 2006, Nature Methods.

[43]  Frederick M. Ausubel,et al.  Distinct Pathogenesis and Host Responses during Infection of C. elegans by P. aeruginosa and S. aureus , 2010, PLoS pathogens.

[44]  S. Brenner The genetics of Caenorhabditis elegans. , 1974, Genetics.

[45]  Colin N. Dewey,et al.  Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures , 2007, Nature.

[46]  Robert Tjian,et al.  Isolation and characterization of the Drosophila gene encoding the TATA box binding protein, TFIID , 1990, Cell.

[47]  N. V. Kirienko,et al.  Transcriptome profiling of the C. elegans Rb ortholog reveals diverse developmental roles. , 2007, Developmental biology.

[48]  D. Rhodes,et al.  Nucleosome cores reconstituted from poly (dA-dT) and the octamer of histones. , 1979, Nucleic acids research.

[49]  J. Widom Short-range order in two eukaryotic genomes: relation to chromosome structure. , 1996, Journal of molecular biology.

[50]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[51]  K. Verstrepen,et al.  Promoter architecture and the evolvability of gene expression , 2009, Journal of biology.

[52]  B. Pugh,et al.  Identification and Distinct Regulation of Yeast TATA Box-Containing Genes , 2004, Cell.

[53]  Avinash Kewalramani,et al.  Abundance, Distribution, and Mutation Rates of Homopolymeric Nucleotide Runs in the Genome of Caenorhabditis elegans , 2004, Journal of Molecular Evolution.

[54]  D. Schlessinger,et al.  Multiple Sp1 sites efficiently drive transcription of the TATA-less promoter of the human glypican 3 (GPC3) gene. , 1998, Gene.

[55]  B. Cairns The logic of chromatin architecture and remodelling at promoters , 2009, Nature.

[56]  D. Thiele,et al.  Functional Analysis of a Homopolymeric (dA-dT) Element That Provides Nucleosomal Access to Yeast and Mammalian Transcription Factors* , 1999, The Journal of Biological Chemistry.

[57]  N. Barkai,et al.  Two strategies for gene regulation by promoter nucleosomes. , 2008, Genome research.

[58]  Farren J. Isaacs,et al.  Phenotypic consequences of promoter-mediated transcriptional noise. , 2006, Molecular cell.

[59]  Yechezkel Kashi,et al.  Three Sequence Rules for Chromatin , 2006, Journal of biomolecular structure & dynamics.

[60]  Lucie N. Hutchins,et al.  C. elegans sequences that control trans-splicing and operon pre-mRNA processing. , 2007, RNA.

[61]  J. Widom,et al.  Poly(dA-dT) Promoter Elements Increase the Equilibrium Accessibility of Nucleosomal DNA Target Sites , 2001, Molecular and Cellular Biology.

[62]  H. Drew,et al.  Sequence periodicities in chicken nucleosome core DNA. , 1986, Journal of molecular biology.

[63]  V. Reinke,et al.  Germline Expression Influences Operon Organization in the Caenorhabditis elegans Genome , 2009, Genetics.

[64]  J. T. Kadonaga,et al.  The RNA polymerase II core promoter - the gateway to transcription. , 2008, Current opinion in cell biology.

[65]  K. Struhl Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Thomas Blumenthal,et al.  RNA Processing and Gene Structure , 1997 .

[67]  Alfonso G. Fernandez,et al.  Oligonucleotide Sequence Motifs as Nucleosome Positioning Signals , 2010, PloS one.