Nucleosome Positioning around Transcription Start Site Correlates with Gene Expression Only for Active Chromatin State in Drosophila Interphase Chromosomes
Abstract
:1. Introduction
2. Results
2.1. Gene Classification by Chromatin States and Expression Measures
- Silent (RPKM = 0, 6972 genes);
- Modest (1 ≤ RPKM ≤ 25, 3718);
- High (RPKM > 25, 3584).
- Tissue-specific (BoE ≤ 6, 5534 genes);
- Modest (6 > BoE ≤ 24, 4278);
- Constitutive (BoE >24, 3942).
2.2. Irrespective to Expression Measures, Nucleosome Arrangement Is Conservative for Active Genes
- the strong nucleosome formation sites downstream TSS;
- the depletion of resistant nucleosome sites upstream TSS;
- the regular ladder of sensitive nucleosomes upstream TSS.
2.3. Correlations between Expression Measures and Nucleosome Positioning
- strongly significant negative CC for resistant nucleosomal sites around TSS [−120; +80] for tissue-specific and modest; moderate negative CC for sensitive nucleosomal sites for tissue-specific [−30; +50] and modest [+10; +70];
- strongly significant positive CC downstream TSS [+70; +200] for tissue-specific and modest;
- moderately significant positive CC for sensitive nucleosomal sites upstream TSS in tissue-specific [−210; −180]) and modest [−160; −150].
3. Discussion
- about 20% of Active genes were either silent or tissue-specific;
- about 40% of Non-Active genes had at least modest RPKM or BoE.
- It was estimated [37] that almost half of the human genome contained regular arrays of nucleosomes that enriched in active chromatin domains. Since the presence of transcription factor (TF) binding sites (BS) strongly supports gene expression, the analysis examined the positioning of nucleosomes around these BS using ChIP-seq data for 35 different TFs. As a result, TF occupancy was closely related to the strength of nucleosome positioning.
- The genome-wide location of nucleosomes during zebrafish embryogenesis indicated that well-positioned nucleosome arrays appeared on thousands of promoters during genome activation [38]. It is important to remember that both models [23,30,33] of chromatin states were based on whole genome profiles of a number of non-histone proteins, i.e., the pattern of BS of these proteins should be different in Active in Non-Active genes.
- The recent analysis of chromatin folding for various epigenetic states of chromatin [39] supported the importance of chromatin state annotation for analysis of genome-wide nucleosome organization. In particular, the classification of genomic domains in Drosophila cells into transcriptionally active, inactive, or Polycomb-repressed states revealed distinct chromatin organizations for each state.
- for Active state potentiates transcription, i.e., a more regular nucleosome arrangement in promoter points to higher expression level and higher number of expressed tissues;
- for Non-Active state does not influence gene expression, i.e., the expression level/breadth and the nucleosome positioning are independent.
4. Materials and Methods
4.1. Whole Genome Data Analysis
4.2. Statistical Analysis
5. Conclusions
- Active genes demonstrated clear pattern of nucleosome arrangement around TSS; the regular nucleosome positioning correlates with the expression level/breadth;
- Non-Active genes did not show such clear specificity in nucleosome positioning; the correlation between the regular nucleosome positioning and expression level or breadth either is absent, not conservative, or shows even the opposite significant trend compared to that of Active genes.
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
4HMM | Four state hidden Markov model |
BoE | Breadth of expression |
MNase | Micrococcal nuclease |
Nuc | Nucleosome |
NDR | Nucleosome-depleted region |
RPKM | Reads per kilobase million |
TSS | Transcription start site |
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Levitsky, V.G.; Zykova, T.Y.; Moshkin, Y.M.; Zhimulev, I.F. Nucleosome Positioning around Transcription Start Site Correlates with Gene Expression Only for Active Chromatin State in Drosophila Interphase Chromosomes. Int. J. Mol. Sci. 2020, 21, 9282. https://doi.org/10.3390/ijms21239282
Levitsky VG, Zykova TY, Moshkin YM, Zhimulev IF. Nucleosome Positioning around Transcription Start Site Correlates with Gene Expression Only for Active Chromatin State in Drosophila Interphase Chromosomes. International Journal of Molecular Sciences. 2020; 21(23):9282. https://doi.org/10.3390/ijms21239282
Chicago/Turabian StyleLevitsky, Victor G., Tatyana Yu. Zykova, Yuri M. Moshkin, and Igor F. Zhimulev. 2020. "Nucleosome Positioning around Transcription Start Site Correlates with Gene Expression Only for Active Chromatin State in Drosophila Interphase Chromosomes" International Journal of Molecular Sciences 21, no. 23: 9282. https://doi.org/10.3390/ijms21239282