Characterization of Z-DNA as a nucleosome-boundary element in yeast Saccharomyces cerevisiae

In this article, the effect of a d(CG) DNA dinucleotide repeat sequence on RNA polymerase II transcription is examined in yeast Saccharomyces cerevisiae. Our previous report shows that a d(CG)n dinucleotide repeat sequence located proximally upstream of the TATA box enhances transcription from a minimal CYC1 promoter in a manner that depends on its surrounding negative supercoiling. Here, we demonstrate that the d(CG)9 repeat sequence stimulates gene activity by forming a Z-DNA secondary structure. Furthermore, the extent of transcriptional enhancement by Z-DNA is promoter-specific and determined by its separation distance relative to the TATA box. The stimulatory effect exerted by promoter proximal Z-DNA is not affected by helical phasing relative to the TATA box, suggesting that Z-DNA effects transcription without interacting with the general transcription machinery by looping-out the intervening DNA. A nucleosome-scanning assay reveals that the d(CG)9 repeat sequence in the Z conformation blocks nucleosome formation, and it is found in the linker DNA with two flanking nucleosomes. This result suggests that Z-DNA formation proximally upstream of a promoter is sufficient to demarcate the boundaries of its neighboring nucleosomes, which produces transcriptionally favorable locations for the TATA box near the nucleosomal DNA-entry site and at dyad positions on the nucleosome. These findings suggest that Z-DNA formation in chromatin is a part of the “genomic code” for nucleosome positioning in vivo.

[1]  T. Simonsson,et al.  G-Quadruplex DNA Structures Variations on a Theme , 2001, Biological chemistry.

[2]  L. J. Peck,et al.  Flipping of cloned d(pCpG)n.d(pCpG)n DNA sequences from right- to left-handed helical structure by salt, Co(III), or negative supercoiling. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[3]  James Allan,et al.  CpG methylation remodels chromatin structure in vitro. , 1997, Journal of molecular biology.

[4]  Jordanka Zlatanova,et al.  Fast, long-range, reversible conformational fluctuations in nucleosomes revealed by single-pair fluorescence resonance energy transfer. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Carmel Reilly,et al.  A determining influence for CpG dinucleotides on nucleosome positioning in vitro. , 2004, Nucleic acids research.

[6]  A. Rich,et al.  Z-DNA-binding proteins can act as potent effectors of gene expression in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Widom,et al.  Nucleosomes facilitate their own invasion , 2004, Nature Structural &Molecular Biology.

[8]  A. Rich,et al.  Biological function of the vaccinia virus Z-DNA-binding protein E3L: gene transactivation and antiapoptotic activity in HeLa cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[9]  K. V. van Holde,et al.  Unusual DNA structures, chromatin and transcription. , 1994, BioEssays : news and reviews in molecular, cellular and developmental biology.

[10]  I. Brukner,et al.  Evidence for opposite groove-directed curvature of GGGCCC and AAAAA sequence elements. , 1993, Nucleic acids research.

[11]  A. Rich,et al.  A computer aided thermodynamic approach for predicting the formation of Z‐DNA in naturally occurring sequences. , 1986, The EMBO journal.

[12]  C. Bustamante,et al.  Rapid spontaneous accessibility of nucleosomal DNA , 2005, Nature Structural &Molecular Biology.

[13]  Kevin Struhl,et al.  Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast. , 2005, Molecular cell.

[14]  Martha Kirby,et al.  Regulation of CSF1 Promoter by the SWI/SNF-like BAF Complex , 2001, Cell.

[15]  Alexander Rich,et al.  Z-DNA: the long road to biological function , 2003, Nature Reviews Genetics.

[16]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[17]  K. Itoh,et al.  BRG1 Interacts with Nrf2 To Selectively Mediate HO-1 Induction in Response to Oxidative Stress , 2006, Molecular and Cellular Biology.

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

[19]  J. Pérez-Ortín,et al.  Analysis of the Structure of a Natural Alternating d(TA)n Sequence in Yeast Chromatin , 1997, Yeast.

[20]  Alfred Nordheim,et al.  Negatively supercoiled plasmids contain left-handed Z-DNA segments as detected by specific antibody binding , 1982, Cell.

[21]  G. F. Joyce,et al.  Directed evolution of nucleic acid enzymes. , 2003, Annual review of biochemistry.

[22]  A. Rich,et al.  Chicken double-stranded RNA adenosine deaminase has apparent specificity for Z-DNA. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Kornberg,et al.  Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome , 1999, Cell.

[24]  Alavattam Sreedhara,et al.  Ligating DNA with DNA. , 2004, Journal of the American Chemical Society.

[25]  S. Silverman,et al.  A DNA enzyme that mimics the first step of RNA splicing , 2004, Nature Structural &Molecular Biology.

[26]  G. Felsenfeld,et al.  Effect of Z-DNA on nucleosome placement. , 1987, Journal of molecular biology.

[27]  K. Zhao,et al.  Cooperative Activity of BRG1 and Z-DNA Formation in Chromatin Remodeling , 2006, Molecular and Cellular Biology.

[28]  E. Adhami.  Calculating the etiology of systemic lupus erythematosus. , 2004, Medical hypotheses.

[29]  J. Blackwell,et al.  Evidence for a functional repeat polymorphism in the promoter of the human NRAMP1 gene that correlates with autoimmune versus infectious disease susceptibility , 1999, Journal of medical genetics.

[30]  A. Rich,et al.  A polymorphic dinucleotide repeat in the rat nucleolin gene forms Z-DNA and inhibits promoter activity , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. Behe,et al.  Effects of methylation on a synthetic polynucleotide: the B--Z transition in poly(dG-m5dC).poly(dG-m5dC). , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Wölfl,et al.  Transcription of human c‐myc in permeabilized nuclei is associated with formation of Z‐DNA in three discrete regions of the gene. , 1992, The EMBO journal.

[33]  K. V. van Holde,et al.  A reexamination of the reported B----Z DNA transition in nucleosomes reconstituted with poly(dG-m5dC).poly(dG-m5dC). , 1987, Biochemistry.

[34]  Tom Misteli,et al.  A non-random walk through the genome , 2005, Genome Biology.

[35]  M. Behe,et al.  Effect of the B--Z transition in poly(dG-m5dC) . poly(dG-m5dC) on nucleosome formation. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Alexander Rich,et al.  Structure of the DLM-1–Z-DNA complex reveals a conserved family of Z-DNA-binding proteins , 2018, Nature Structural Biology.