A computational approach to map nucleosome positions and alternative chromatin states with base pair resolution
- Harvard University, United States
- Harvard University, USA
- Howard Hughes Medical Institute, Harvard University, United States
- The Broad Institute of MIT and Harvard, United States
Figures
Figure 1 with 2 supplements
Illustration of the Template-Based Bayesian (TBB) approach for determining nucleosome positions.
(A) Diagram illustrating the heterogeneous nucleosome positions and the consensus centers of nucleosomes along a genomic region in a population of cells. Blue ovals illustrate individual nucleosomes …
Figure 1—figure supplement 1
Diagrams of nucleosome digestion variability template estimation.
Diagrams illustrating the estimation of the nucleosome digestion variability template from the length distribution of paired-end sequencing reads. The length of a sequenced DNA fragment is …
Figure 1—figure supplement 2
Length distribution of nucleosome reads.
Plots showing the length distribution of paired-end sequencing reads within gene coding regions and non-coding regions (left), and in the promoters of genes and non-promoter regions (right).
Figure 2 with 6 supplements
Genome-wide evaluation of the TBB approach and alternative nucleosome positions.
Histogram of the nearest distance: (A) between the consensus centers of nucleosomes determined by the TBB approach and by the Parzen window approach; (B) between the consensus centers determined by …
Figure 2—figure supplement 1
Titration of MNase digestion.
(A–C) Titration of MNase digestion for obtaining mononucleosomes. T0, T1, T2 and T3 correspond to MNase digestion with 0.5U, 1U, 2U and 4U MNase. (A) Bioanalyzer analysis of purified nucleosomal DNA …
Figure 2—figure supplement 2
Cumulative distribution of the nearest distance analysis in Figure 2A.
Cumulative distribution of the nearest distance between the consensus centers of nucleosomes determined by the TBB approach and by the Parzen window approach. Circles mark the distance that matches …
Figure 2—figure supplement 3
Cumulative distribution of the nearest distance analysis in Figure 2B.
Red traces and gray traces show the cumulative distribution of the nearest distance between the consensus centers determined by the TBB approach (red) or randomly generated consensus centers (gray) …
Figure 2—figure supplement 4
Cumulative distribution of the nearest distance analysis in Figure 2C.
Magenta traces and gray traces show the cumulative distribution of the nearest distance between the TBB nucleosome positions (magenta) or randomly generated nucleosome positions (gray) and the …
Figure 2—figure supplement 5
Cumulative distribution of the nearest distance analysis in Figure 2D.
Green traces and gray traces show the cumulative distribution of the nearest distance between between the TBB consensus centers (green) or randomly generated consensus centers (gray) mapped in two …
Figure 2—figure supplement 6
Cumulative distribution of the nearest distance analysis in Figure 2E.
Blue traces and gray traces show the cumulative distribution of the nearest distance between between the TBB nucleosome positions (Blue) or randomly generated nucleosome positions (gray) mapped in …
Figure 3
Nucleosome detection from in silico MNase-seq datasets.
(A) Plots summarizing the distance between the detected TBB nucleosome positions in the in silico datasets and the nearest simulated primary and alternative nucleosome positions. ('C', total …
Figure 4 with 4 supplements
Dinucleotides frequency of nucleosome positions.
(A–C) Normalized frequency of AA/AT/TA/TT and CC/CG/GC/GG dinucleotides of DNA sequences aligned at the centers of nucleosomes, for all TBB nucleosome positions in yeast, both before (A) and after (C…
Figure 4—figure supplement 1
Dinucleotides frequency of nucleosome consensus centers.
(left) Dinucleotide frequency for all 62,035 consensus centers of nucleosomes identified in experiment T1. (right) Dinucleotide frequency for all consensus centers of nucleosomes identified on human …
Figure 4—figure supplement 2
Dinucleotides frequency of selected 147 bp nucleosome reads.
(left) Dinucleotide frequency for 62,035 randomly selected sequence fragments that are exactly 147 bp in length in experiment T1. (right) Dinucleotide frequency for all human nucleosome reads that …
Figure 4—figure supplement 3
Dinucleotides frequency of TBB positions.
Dinucleotide frequency for 62,035 (the same number as consensus centers) randomly selected TBB nucleosome positions from experiment T1.
Figure 4—figure supplement 4
MNase-digestion correction for dinucleotides frequency of TBB positions.
Dinucleotide frequency for TBB positions from experiment T1(blue, pink) and the nucleosome positions determined from the simulated MNase digestion data set (gray).
Figure 5 with 2 supplements
Alternatively positioned nucleosomes at transcription start sites.
(A,B) Examples of a uniquely positioned nucleosome (A), and alternatively positioned nucleosomes at the TSS (B). Blue and magenta traces show the sequencing read midpoint occupancy and fitted …
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Figure 5—source data 1
Source data for Figure 5C, with arrays of positions, midpoints from T1 and T2 used for generating the graph.
- https://doi.org/10.7554/eLife.16970.020
Figure 5—figure supplement 1
Reads occupancy between alternatively positioned nucleosomes.
Bar graphs showing the ratios of the reads corresponding to alternatively positioned nucleosomes. The genes are the same as the panels in Figure 5C from the top to the bottom. Numbers on top of each …
Figure 5—figure supplement 2
Heat map showing the TBB nucleosome positions and the midpoint read occupancy.
(A) Heatmaps are the same as Figure 5C, except that the position clusters with more than 2 positions are excluded. (B) Plots show the average midpoint occupancy of genes in groups of 1000. (C) Bar …
Figure 6
Alternatively positioned nucleosomes and transcription pre-initiation complex.
(A) Plots (left) showing the locations of TSSs relative to the average centers of all overlapping TBB nucleosome positions shown in Figure 3C ('All', black) to uniquely positioned nucleosomes …
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Figure 6—source data 1
Source data for Figure 6, with genes and coordinates of TSSs, unique, proximal and distal nucleosome positions.
- https://doi.org/10.7554/eLife.16970.024
Figure 7
Sequence features of uniquely and alternatively positioned nucleosomes.
(A) Plots showing the frequency of AA/AT/TA/TT and CC/CG/GC/GG dinucleotides of DNA sequences aligned at the TBB nucleosome positions of either unique, proximal or distal nucleosomes at gene …
Author response image 1
Cumulative distribution of the nearest distance analysis for TBB positions around gene TSSs.
The curves show the cumulative distribution of the nearest distance between the TBB nucleosome positions at gene TSSs analyzed for Figure 5C and the nucleosome positions mapped by the chemical …
Author response image 2
Significance of the enrichment in uniquely positioned nucleosomes among genes stratified by expression level determined in Newman et al.
https://doi.org/10.7554/eLife.16970.030
Author response image 3
Significance of the enrichment in uniquely positioned nucleosomes among genes stratified by expression level determined in Zid et al.
https://doi.org/10.7554/eLife.16970.031Additional files
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Supplementary file 1
A compressed file containing the TBB nucleosome positions and the TBB consensus centers of nucleosomes for yeast data sets ‘T1’, ‘T2’, and human chromosome 12, position 38,000,000–48,000,000.
- https://doi.org/10.7554/eLife.16970.026
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Supplementary file 2
Cumulative distribution of the distance between in silico TBB positions and matched primary positions (2A) or matched alternative positions (2B) from in silico experiments.
- https://doi.org/10.7554/eLife.16970.027
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Supplementary file 3
A table comparison of published methods for determining nucleosome positions.
- https://doi.org/10.7554/eLife.16970.028
