Figure 3.
Monocyte subsets are primed epigenetically at the level of progenitor cells. (A) PCA plot of chromatin accessibility at ATAC-seq peaks in progenitors, and monocyte ATAC-seq reveals distinct patterns of chromatin accessibility among myeloid progenitors. (B) PCA of chromatin accessibility patterns in progenitors, with points colored based on functional classes of monocytes. (C) Representative genomic tracks of ATAC-seq tag density near cKit and CD11b genes with similar chromatin accessibility across all classes (boxed). (D) Representative genomic tracks of differential ATAC-seq tag density between classes (boxed). (E) Gene expression is associated with chromatin openness in myeloid progenitors. Plots of genome-wide chromatin accessibility were calculated as moving averages of ATAC-seq signal in a sliding window (window size, 55; bin size, 1), sorted based on gene expression. (F) Scatter plots of genome-wide RNA expression differences against promoter chromatin accessibility differences between class 1 and class 2 as a representative example. Each gene is represented by a point in the space of log2 of fold change between average RNA-seq reads per kilobase million (RPKM) values among the clones of each class (x-axis) against log2 of fold change between average ATAC-seq RPKM values calculated at the transcription start site (TSS) proximal region among the clones of each class (y-axis). (G) Representative genomic tracks of class-specific differences in enhancer chromatin accessibility among myeloid progenitors that precede the corresponding class-specific differences in gene expression among mature monocytes. For Bcl6 gene, multiple pairwise differences between classes were detected, and representative clones for all 4 classes are shown. For Bach1 and Fos, 1 class pair showed a difference: class 1 vs 2 and class 2 vs 3, respectively. Representative tracks for these class pairs are shown. (H) Class-specific monocyte expression signatures preceded by progenitor enhancer differences are enriched in key functional gene categories. (I) Enriched TF binding motifs among progenitor enhancers with class-specific differential ATAC-seq peaks that precede class-specific monocyte gene expression.

Monocyte subsets are primed epigenetically at the level of progenitor cells. (A) PCA plot of chromatin accessibility at ATAC-seq peaks in progenitors, and monocyte ATAC-seq reveals distinct patterns of chromatin accessibility among myeloid progenitors. (B) PCA of chromatin accessibility patterns in progenitors, with points colored based on functional classes of monocytes. (C) Representative genomic tracks of ATAC-seq tag density near cKit and CD11b genes with similar chromatin accessibility across all classes (boxed). (D) Representative genomic tracks of differential ATAC-seq tag density between classes (boxed). (E) Gene expression is associated with chromatin openness in myeloid progenitors. Plots of genome-wide chromatin accessibility were calculated as moving averages of ATAC-seq signal in a sliding window (window size, 55; bin size, 1), sorted based on gene expression. (F) Scatter plots of genome-wide RNA expression differences against promoter chromatin accessibility differences between class 1 and class 2 as a representative example. Each gene is represented by a point in the space of log2 of fold change between average RNA-seq reads per kilobase million (RPKM) values among the clones of each class (x-axis) against log2 of fold change between average ATAC-seq RPKM values calculated at the transcription start site (TSS) proximal region among the clones of each class (y-axis). (G) Representative genomic tracks of class-specific differences in enhancer chromatin accessibility among myeloid progenitors that precede the corresponding class-specific differences in gene expression among mature monocytes. For Bcl6 gene, multiple pairwise differences between classes were detected, and representative clones for all 4 classes are shown. For Bach1 and Fos, 1 class pair showed a difference: class 1 vs 2 and class 2 vs 3, respectively. Representative tracks for these class pairs are shown. (H) Class-specific monocyte expression signatures preceded by progenitor enhancer differences are enriched in key functional gene categories. (I) Enriched TF binding motifs among progenitor enhancers with class-specific differential ATAC-seq peaks that precede class-specific monocyte gene expression.

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