Yang Doo, Ioshikhes Ilya
1 Ottawa Institute of Systems Biology, University of Ottawa , Ottawa, Ontario, Canada .
2 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa , Ottawa, Ontario, Canada .
J Comput Biol. 2017 Apr;24(4):289-298. doi: 10.1089/cmb.2016.0173. Epub 2016 Dec 19.
Nucleosomes are implicated in transcriptional regulation as well as in packing and stabilizing the DNA. Nucleosome positions affect the transcription by impeding or facilitating the binding of transcription factors. The DNA sequence, especially the periodic occurrences of dinucleotides, is a major factor that affects the nucleosome positioning. We analyzed the Drosophila DNA sequences bound by H2A and H2A.Z nucleosomes. Periodic patterns of dinucleotides (weak-weak/strong-strong or purine-purine/pyrimidine-pyrimidine) were identified as WW/SS and RR/YY nucleosome positioning sequence (NPS) patterns. The WW/SS NPS pattern of the H2A nucleosome has a 10-bp period of weak-weak/strong-strong (W = A or T; S = G or C) dinucleotides. The 10-bp periodicity, however, is disrupted in the middle of the sequence. At the dyad, the SS dinucleotide is preferred. On the other hand, the RR/YY NPS pattern has an 18-bp periodicity of purine-purine/pyrimidine-pyrimidine (R = A or G; Y = T or C) dinucleotides. The NPS patterns from H2A.Z nucleosomes differ from the NPS patterns from H2A nucleosomes. The RR/YY pattern of H2A.Z nucleosomes has major peaks shifted by 10 bp deviated from the H2A nucleosome pattern. The H2A and H2A.Z nucleosomes have different sequence preferences. The shifted peaks coincide with DNA regions interacting with the histone loops.
核小体与转录调控以及DNA的包装和稳定有关。核小体位置通过阻碍或促进转录因子的结合来影响转录。DNA序列,尤其是二核苷酸的周期性出现,是影响核小体定位的主要因素。我们分析了与H2A和H2A.Z核小体结合的果蝇DNA序列。二核苷酸的周期性模式(弱-弱/强-强或嘌呤-嘌呤/嘧啶-嘧啶)被确定为WW/SS和RR/YY核小体定位序列(NPS)模式。H2A核小体的WW/SS NPS模式具有10个碱基对的弱-弱/强-强(W = A或T;S = G或C)二核苷酸周期。然而,10个碱基对的周期性在序列中间被破坏。在二分体处,SS二核苷酸是首选。另一方面,RR/YY NPS模式具有18个碱基对的嘌呤-嘌呤/嘧啶-嘧啶(R = A或G;Y = T或C)二核苷酸周期。H2A.Z核小体的NPS模式与H2A核小体的NPS模式不同。H2A.Z核小体的RR/YY模式的主要峰与H2A核小体模式相比偏移了10个碱基对。H2A和H2A.Z核小体具有不同的序列偏好。偏移的峰与与组蛋白环相互作用的DNA区域重合。