Genomic Approaches for Determining Nucleosome Occupancy in Yeast

2011 ◽  
pp. 389-411 ◽  
Author(s):  
Kyle Tsui ◽  
Tanja Durbic ◽  
Marinella Gebbia ◽  
Corey Nislow
Keyword(s):  
Nucleosome Occupancy

scholarly journals A deformation energy model reveals sequence-dependent property of nucleosome positioning

Chromosoma ◽  
2021 ◽  
Vol 130 (1) ◽  
pp. 27-40
Author(s):  
Guoqing Liu ◽  
Hongyu Zhao ◽  
Hu Meng ◽  
Yongqiang Xing ◽  
Lu Cai
Keyword(s):  
Budding Yeast ◽  
Nucleosome Occupancy ◽  
Nucleosome Positioning ◽  
Deformation Energy ◽  
Energy Model ◽  
Structural Parameter ◽  
High Deformation ◽  
Dna Deformation ◽  
Genome Wide ◽  
Genomic Regions

AbstractWe present a deformation energy model for predicting nucleosome positioning, in which a position-dependent structural parameter set derived from crystal structures of nucleosomes was used to calculate the DNA deformation energy. The model is successful in predicting nucleosome occupancy genome-wide in budding yeast, nucleosome free energy, and rotational positioning of nucleosomes. Our model also indicates that the genomic regions underlying the MNase-sensitive nucleosomes in budding yeast have high deformation energy and, consequently, low nucleosome-forming ability, while the MNase-sensitive non-histone particles are characterized by much lower DNA deformation energy and high nucleosome preference. In addition, we also revealed that remodelers, SNF2 and RSC8, are likely to act in chromatin remodeling by binding to broad nucleosome-depleted regions that are intrinsically favorable for nucleosome positioning. Our data support the important role of position-dependent physical properties of DNA in nucleosome positioning.

scholarly journals Nested plant LTR retrotransposons target specific regions of other elements, while all LTR retrotransposons often target palindromes and nucleosome-occupied regions: in silico study

Mobile DNA ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Pavel Jedlicka ◽  
Matej Lexa ◽  
Ivan Vanat ◽  
Roman Hobza ◽  
Eduard Kejnovsky
Keyword(s):  
Secondary Structure ◽  
In Silico ◽  
Negative Impact ◽  
Nucleosome Occupancy ◽  
Ltr Retrotransposons ◽  
Sequence Composition ◽  
Plant Genomes ◽  
Weak Preference ◽  
In Silico Study ◽  
Impact On Family

Abstract Background Nesting is common in LTR retrotransposons, especially in large genomes containing a high number of elements. Results We analyzed 12 plant genomes and obtained 1491 pairs of nested and original (pre-existing) LTR retrotransposons. We systematically analyzed mutual nesting of individual LTR retrotransposons and found that certain families, more often belonging to the Ty3/gypsy than Ty1/copia superfamilies, showed a higher nesting frequency as well as a higher preference for older copies of the same family (“autoinsertions”). Nested LTR retrotransposons were preferentially located in the 3’UTR of other LTR retrotransposons, while coding and regulatory regions (LTRs) are not commonly targeted. Insertions displayed a weak preference for palindromes and were associated with a strong positional pattern of higher predicted nucleosome occupancy. Deviation from randomness in target site choice was also found in 13,983 non-nested plant LTR retrotransposons. Conclusions We reveal that nesting of LTR retrotransposons is not random. Integration is correlated with sequence composition, secondary structure and the chromatin environment. Insertion into retrotransposon positions with a low negative impact on family fitness supports the concept of the genome being viewed as an ecosystem of various elements.

scholarly journals Different SP1 binding dynamics at individual genomic loci in human cells

2020 ◽  
Author(s):  
Yuko Hasegawa ◽  
Kevin Struhl
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Time Course ◽  
Nucleosome Occupancy ◽  
Binding Kinetics ◽  
Common Mechanism ◽  
Sequence Motif ◽  
Promoter Regions ◽  
Pml Bodies ◽  
Slow Turnover

Using a tamoxifen-inducible time-course ChIP-seq approach, we show that the ubiquitous transcription factor SP1 has different binding dynamics at its target sites in the human genome that are not correlated with SP1 occupancy levels at those sites. While ~70% of SP1 binding sites are located in promoter regions, loci with slow SP1 binding turnover are enriched in enhancer and Polycomb-repressed regions. Unexpectedly, SP1 sites with fast turnover times tend to have higher quality and more copies of the SP1 sequence motif. Different co-binding factors associate near SP1 binding sites depending on their binding kinetics and on their location at promoters or enhancers. For example, NFY and FOS are preferentially associated near promoter-bound SP1 sites with fast turnover, whereas DNA motifs of ETS and homeodomain proteins are preferentially observed at sites with slow turnover. At promoters but not enhancers, proteins involved in sumoylation and PML bodies associate more strongly with slow SP1 binding sites than with the fast-binding sites. The speed of SP1 binding turnover is not associated with nucleosome occupancy, and it is not necessarily coupled to higher transcriptional activity. These results with SP1 are in contrast from those of human TBP, indicating that there is no common mechanism affecting transcription factor binding kinetics.

scholarly journals Centromeric DNA destabilizes H3 nucleosomes to promote CENP-A deposition during the cell cycle

2017 ◽  
Author(s):  
Manu Shukla ◽  
Tong Pin ◽  
Sharon A. White ◽  
Puneet P. Singh ◽  
Angus M. Reid ◽  
...  
Keyword(s):  
Feedback Loop ◽  
Chromosomal Location ◽  
Nucleosome Occupancy ◽  
Histone H3 ◽  
S Phase ◽  
Intrinsic Properties ◽  
Centromeric Dna ◽  
Kinetochore Assembly ◽  
Histone H3 Variant ◽  
Specific Sequences

SummaryActive centromeres are defined by the presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location CENP-A chromatin and kinetochores are maintained at that location though a positive feedback loop where kinetochore proteins recruited by CENP-A itself promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences. Intrinsic properties of centromeric DNA may favour the assembly of CENP-A rather than H3 nucleosomes. Here we investigate histone dynamics on centromeric DNA. We show that during S-phase histone H3 is deposited as a placeholder at fission yeast centromeres and is subsequently evicted in G2 when we detect deposition of the majority of new CENP-ACnp1. We also find that centromeric DNA has an innate property of driving high rates of turnover of H3 containing nucleosomes resulting in low nucleosome occupancy. When placed at an ectopic chromosomal location in the absence of any CENP-ACnp1 assembly, centromeric DNA retains its ability to impose S-phase deposition and G2 eviction of H3, suggesting that features within this DNA program H3 dynamics. As RNAPII occupancy on this centromere DNA coincides with H3 eviction in G2, we propose a model in which RNAPII-coupled chromatin remodelling promotes replacement of H3 with CENP-ACnp1 nucleosomes.

scholarly journals Different SP1 binding dynamics at individual genomic loci in human cells

2021 ◽  
Vol 118 (46) ◽  
pp. e2113579118
Author(s):  
Yuko Hasegawa ◽  
Kevin Struhl
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Time Course ◽  
Nucleosome Occupancy ◽  
Binding Kinetics ◽  
Common Mechanism ◽  
Sequence Motif ◽  
Chip Sequencing ◽  
Target Sites ◽  
Maximal Binding

Using a tamoxifen-inducible time-course ChIP-sequencing (ChIP-seq) approach, we show that the ubiquitous transcription factor SP1 has different binding dynamics at its target sites in the human genome. SP1 very rapidly reaches maximal binding levels at some sites, but binding kinetics at other sites is biphasic, with rapid half-maximal binding followed by a considerably slower increase to maximal binding. While ∼70% of SP1 binding sites are located at promoter regions, loci with slow SP1 binding kinetics are enriched in enhancer and Polycomb-repressed regions. Unexpectedly, SP1 sites with fast binding kinetics tend to have higher quality and more copies of the SP1 sequence motif. Different cobinding factors associate near SP1 binding sites depending on their binding kinetics and on their location at promoters or enhancers. For example, NFY and FOS are preferentially associated near promoter-bound SP1 sites with fast binding kinetics, whereas DNA motifs of ETS and homeodomain proteins are preferentially observed at sites with slow binding kinetics. At promoters but not enhancers, proteins involved in sumoylation and PML bodies associate more strongly with slow SP1 binding sites than with the fast binding sites. The speed of SP1 binding is not associated with nucleosome occupancy, and it is not necessarily coupled to higher transcriptional activity. These results with SP1 are in contrast to those of human TBP, indicating that there is no common mechanism affecting transcription factor binding kinetics. The biphasic kinetics at some SP1 target sites suggest the existence of distinct chromatin states at these loci in different cells within the overall population.

scholarly journals Haplotype-aware single-cell multiomics uncovers functional effects of somatic structural variation

2021 ◽  
Author(s):  
Hyobin Jeong ◽  
Karen Grimes ◽  
Peter-Martin Bruch ◽  
Tobias Rausch ◽  
Patrick Hasenfeld ◽  
...  
Keyword(s):  
Single Cell ◽  
Nucleosome Occupancy ◽  
Single Cells ◽  
Chromosomal Rearrangements ◽  
Regulatory Elements ◽  
Computational Method ◽  
Tumour Heterogeneity ◽  
Cancer Genomes ◽  
Functional Consequences ◽  
Oncogenic Transcription Factor

Somatic structural variants (SVs) are widespread in cancer genomes, however, their impact on tumorigenesis and intra-tumour heterogeneity is incompletely understood, since methods to functionally characterize the broad spectrum of SVs arising in cancerous single-cells are lacking. We present a computational method, scNOVA, that couples SV discovery with nucleosome occupancy analysis by haplotype-resolved single-cell sequencing, to systematically uncover SV effects on cis-regulatory elements and gene activity. Application to leukemias and cell lines uncovered SV outcomes at several loci, including dysregulated cancer-related pathways and mono-allelic oncogene expression near SV breakpoints. At the intra-patient level, we identified different yet overlapping subclonal SVs that converge on aberrant Wnt signaling. We also deconvoluted the effects of catastrophic chromosomal rearrangements resulting in oncogenic transcription factor dysregulation. scNOVA directly links SVs to their functional consequences, opening the door for single-cell multiomics of SVs in heterogeneous cell populations.

scholarly journals A Deep-Learning Pipeline for TSS Coverage Imputation From Shallow Cell-Free DNA Sequencing

2021 ◽  
Vol 8 ◽  
Author(s):  
Bo-Wei Han ◽  
Xu Yang ◽  
Shou-Fang Qu ◽  
Zhi-Wei Guo ◽  
Li-Min Huang ◽  
...  
Keyword(s):  
Deep Learning ◽  
Nucleosome Occupancy ◽  
Sequencing Data ◽  
Cell Free Dna ◽  
Transcription Start Sites ◽  
Free Dna ◽  
Coverage Accuracy ◽  
Moderate Cost ◽  
Coverage Profile ◽  
High Depth

Cell-free DNA (cfDNA) serves as a footprint of the nucleosome occupancy status of transcription start sites (TSSs), and has been subject to wide development for use in noninvasive health monitoring and disease detection. However, the requirement for high sequencing depth limits its clinical use. Here, we introduce a deep-learning pipeline designed for TSS coverage profiles generated from shallow cfDNA sequencing called the Autoencoder of cfDNA TSS (AECT) coverage profile. AECT outperformed existing single-cell sequencing imputation algorithms in terms of improvements to TSS coverage accuracy and the capture of latent biological features that distinguish sex or tumor status. We built classifiers for the detection of breast and rectal cancer using AECT-imputed shallow sequencing data, and their performance was close to that achieved by high-depth sequencing, suggesting that AECT could provide a broadly applicable noninvasive screening approach with high accuracy and at a moderate cost.

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