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Thermogenomic Analysis of Left-Handed Z-DNA Propensities in Genomes

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Z-DNA

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2651))

Abstract

The initial discovery of left-handed Z-DNA was met with great excitement as a dramatic alternative to the right-handed double-helical conformation of canonical B-DNA. In this chapter, we describe the workings of the program ZHUNT as a computational approach to mapping Z-DNA in genomic sequences using a rigorous thermodynamic model for the transition between the two conformations (the B–Z transition). The discussion starts with a brief summary of the structural properties that differentiate Z- from B-DNA, focusing on those properties that are particularly relevant to the B–Z transition and the junction that splices a left- to right-handed DNA duplex. We then derive the statistical mechanics (SM) analysis of the zipper model that describes the cooperative B–Z transition and show that this analysis very accurately simulates this behavior of naturally occurring sequences that are induced to undergo the B–Z transition through negative supercoiling. A description of the ZHUNT algorithm and its validation are presented, followed by how the program had been applied for genomic and phylogenomic analyses in the past and how a user can access the online version of the program. Finally, we present a new version of ZHUNT (called mZHUNT) that has been parameterized to analyze sequences that contain 5-methylcytosine bases and compare the results of the ZHUNT and mZHUNT analyses on native and methylated yeast chromosome 1.

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Acknowledgments

The studies in Ho laboratory were supported by a grant from the National Science Foundation (CHE-1905328 and MCB-2124202). We thank A. N. Ho for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO, USA

    Ryan S. Czarny & P. Shing Ho

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  1. Ryan S. Czarny
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  2. P. Shing Ho
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Correspondence to P. Shing Ho .

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Editors and Affiliations

  1. Department of Precision Medicine, Institute for Antimicrobial Resistance Research and Therapeutics, Sungkyunkwan University School of Medicine, Suwon, Korea (Republic of)

    Kyeong Kyu Kim

  2. Department of Precision Medicine, Institute for Antimicrobial Resistance Research and Therapeutics, Sungkyunkwan University School of Medicine, Suwon, Korea (Republic of)

    Vinod Kumar Subramani

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Czarny, R.S., Ho, P.S. (2023). Thermogenomic Analysis of Left-Handed Z-DNA Propensities in Genomes. In: Kim, K.K., Subramani, V.K. (eds) Z-DNA. Methods in Molecular Biology, vol 2651. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3084-6_14

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  • DOI: https://doi.org/10.1007/978-1-0716-3084-6_14

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3083-9

  • Online ISBN: 978-1-0716-3084-6

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