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Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.

Nag A, Vigneau S, Savova V, Zwemer LM, Gimelbrant AA - G3 (Bethesda) (2015)

Bottom Line: Recently, we reported that a specific histone modification signature is strongly associated with MAE and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells.Our analyses reveal extensive conservation in the identity of MAE genes between the two species.By analyzing MAE chromatin signature in a large number of cell and tissue types, we show that it remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute; and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02215.

No MeSH data available.


Chromatin signature is an informative proxy of mosaic monoallelic expression (MAE) in mouse cells from different lineages. (A) MAE state was inferred for genes with a particular combination of gene body signal for H3K27me3 and H3K36me3 ChIP-Seq, by applying the MaGIC pipeline in Abelson lymphoblast clone 1 from 129Sv/ImJ × CAST/EiJ F1 mouse (GSE67384; Table S1 and Table S2). Red line demarcates the area the classifier recognizes as being enriched with MAE genes (see Materials and Methods). Genes (represented as dots) are colored according to allelic expression analysis in the same clonal cell line: monoallelic (blue) or biallelic (gold) (Table S3). Genes with indeterminate allelic bias are shown as gray dots. The accuracy of the inference is summarized in the right panel, where genes are called monoallelic (blue) or biallelic (gold) on the basis of allele-specific analysis of RNA-Seq. (B−D) Same analysis as in (A), but with different sources of ChIP-Seq and RNA-Seq data, as indicated. (B) ChIP-Seq and RNA abundance data used in MaGIC pipeline were from CD43− B cells (GSE31039; Table S1 and Table S2), and allele-specific RNA-Seq analysis was performed on two independent clonal cell lines from 129Sv/ImJ × CAST/EiJ F1 mice: Abl.1 and Abl.2 (GSE67384; Table S1 and Table S3; see main text for details). (C) ChIP-Seq and RNA abundance data from MEF cells (GSE12241; Table S1 and Table S2); allele-specific RNA-Seq analysis on two fibroblast clonal lines from 129Sv/ImJ × CAST/EiJ F1 mice: Fib.1 and Fib.2 (GSE67384; Table S1 and Table S3; see main text). (D) ChIP-Seq and RNA abundance data from neuronal progenitor cells (GSE33252; Table S1 and Table S2); allele-specific RNA-Seq analysis on eight clonal neuronal progenitor cell lines from 129Sv/ImJ × CAST/EiJ F1 mice (GSE54016; Table S1 and Table S3; see main text).
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fig1: Chromatin signature is an informative proxy of mosaic monoallelic expression (MAE) in mouse cells from different lineages. (A) MAE state was inferred for genes with a particular combination of gene body signal for H3K27me3 and H3K36me3 ChIP-Seq, by applying the MaGIC pipeline in Abelson lymphoblast clone 1 from 129Sv/ImJ × CAST/EiJ F1 mouse (GSE67384; Table S1 and Table S2). Red line demarcates the area the classifier recognizes as being enriched with MAE genes (see Materials and Methods). Genes (represented as dots) are colored according to allelic expression analysis in the same clonal cell line: monoallelic (blue) or biallelic (gold) (Table S3). Genes with indeterminate allelic bias are shown as gray dots. The accuracy of the inference is summarized in the right panel, where genes are called monoallelic (blue) or biallelic (gold) on the basis of allele-specific analysis of RNA-Seq. (B−D) Same analysis as in (A), but with different sources of ChIP-Seq and RNA-Seq data, as indicated. (B) ChIP-Seq and RNA abundance data used in MaGIC pipeline were from CD43− B cells (GSE31039; Table S1 and Table S2), and allele-specific RNA-Seq analysis was performed on two independent clonal cell lines from 129Sv/ImJ × CAST/EiJ F1 mice: Abl.1 and Abl.2 (GSE67384; Table S1 and Table S3; see main text for details). (C) ChIP-Seq and RNA abundance data from MEF cells (GSE12241; Table S1 and Table S2); allele-specific RNA-Seq analysis on two fibroblast clonal lines from 129Sv/ImJ × CAST/EiJ F1 mice: Fib.1 and Fib.2 (GSE67384; Table S1 and Table S3; see main text). (D) ChIP-Seq and RNA abundance data from neuronal progenitor cells (GSE33252; Table S1 and Table S2); allele-specific RNA-Seq analysis on eight clonal neuronal progenitor cell lines from 129Sv/ImJ × CAST/EiJ F1 mice (GSE54016; Table S1 and Table S3; see main text).

Mentions: In Abl.1 clone, 4077 genes were assessable as either MAE or BAE by the use of both chromatin signature and allelic expression data. Of 492 genes classified as MAE with MaGIC, 73% were confirmed as true positive by RNA-Seq analysis, whereas of the remaining 3585 genes classified as BAE, 75% were confirmed as true negative [Figure 1A, Table S2, and Table S3; Fisher exact P < 2.2E-16; odds ratio (OR) = 8.2]. We conclude that the H3K27me3/H3K36me3 gene body chromatin signature is an informative proxy of monoallelic expression in mouse clonal B lymphoid cells and the MaGIC pipeline is up to 73% accurate for inferring MAE.


Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.

Nag A, Vigneau S, Savova V, Zwemer LM, Gimelbrant AA - G3 (Bethesda) (2015)

Chromatin signature is an informative proxy of mosaic monoallelic expression (MAE) in mouse cells from different lineages. (A) MAE state was inferred for genes with a particular combination of gene body signal for H3K27me3 and H3K36me3 ChIP-Seq, by applying the MaGIC pipeline in Abelson lymphoblast clone 1 from 129Sv/ImJ × CAST/EiJ F1 mouse (GSE67384; Table S1 and Table S2). Red line demarcates the area the classifier recognizes as being enriched with MAE genes (see Materials and Methods). Genes (represented as dots) are colored according to allelic expression analysis in the same clonal cell line: monoallelic (blue) or biallelic (gold) (Table S3). Genes with indeterminate allelic bias are shown as gray dots. The accuracy of the inference is summarized in the right panel, where genes are called monoallelic (blue) or biallelic (gold) on the basis of allele-specific analysis of RNA-Seq. (B−D) Same analysis as in (A), but with different sources of ChIP-Seq and RNA-Seq data, as indicated. (B) ChIP-Seq and RNA abundance data used in MaGIC pipeline were from CD43− B cells (GSE31039; Table S1 and Table S2), and allele-specific RNA-Seq analysis was performed on two independent clonal cell lines from 129Sv/ImJ × CAST/EiJ F1 mice: Abl.1 and Abl.2 (GSE67384; Table S1 and Table S3; see main text for details). (C) ChIP-Seq and RNA abundance data from MEF cells (GSE12241; Table S1 and Table S2); allele-specific RNA-Seq analysis on two fibroblast clonal lines from 129Sv/ImJ × CAST/EiJ F1 mice: Fib.1 and Fib.2 (GSE67384; Table S1 and Table S3; see main text). (D) ChIP-Seq and RNA abundance data from neuronal progenitor cells (GSE33252; Table S1 and Table S2); allele-specific RNA-Seq analysis on eight clonal neuronal progenitor cell lines from 129Sv/ImJ × CAST/EiJ F1 mice (GSE54016; Table S1 and Table S3; see main text).
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fig1: Chromatin signature is an informative proxy of mosaic monoallelic expression (MAE) in mouse cells from different lineages. (A) MAE state was inferred for genes with a particular combination of gene body signal for H3K27me3 and H3K36me3 ChIP-Seq, by applying the MaGIC pipeline in Abelson lymphoblast clone 1 from 129Sv/ImJ × CAST/EiJ F1 mouse (GSE67384; Table S1 and Table S2). Red line demarcates the area the classifier recognizes as being enriched with MAE genes (see Materials and Methods). Genes (represented as dots) are colored according to allelic expression analysis in the same clonal cell line: monoallelic (blue) or biallelic (gold) (Table S3). Genes with indeterminate allelic bias are shown as gray dots. The accuracy of the inference is summarized in the right panel, where genes are called monoallelic (blue) or biallelic (gold) on the basis of allele-specific analysis of RNA-Seq. (B−D) Same analysis as in (A), but with different sources of ChIP-Seq and RNA-Seq data, as indicated. (B) ChIP-Seq and RNA abundance data used in MaGIC pipeline were from CD43− B cells (GSE31039; Table S1 and Table S2), and allele-specific RNA-Seq analysis was performed on two independent clonal cell lines from 129Sv/ImJ × CAST/EiJ F1 mice: Abl.1 and Abl.2 (GSE67384; Table S1 and Table S3; see main text for details). (C) ChIP-Seq and RNA abundance data from MEF cells (GSE12241; Table S1 and Table S2); allele-specific RNA-Seq analysis on two fibroblast clonal lines from 129Sv/ImJ × CAST/EiJ F1 mice: Fib.1 and Fib.2 (GSE67384; Table S1 and Table S3; see main text). (D) ChIP-Seq and RNA abundance data from neuronal progenitor cells (GSE33252; Table S1 and Table S2); allele-specific RNA-Seq analysis on eight clonal neuronal progenitor cell lines from 129Sv/ImJ × CAST/EiJ F1 mice (GSE54016; Table S1 and Table S3; see main text).
Mentions: In Abl.1 clone, 4077 genes were assessable as either MAE or BAE by the use of both chromatin signature and allelic expression data. Of 492 genes classified as MAE with MaGIC, 73% were confirmed as true positive by RNA-Seq analysis, whereas of the remaining 3585 genes classified as BAE, 75% were confirmed as true negative [Figure 1A, Table S2, and Table S3; Fisher exact P < 2.2E-16; odds ratio (OR) = 8.2]. We conclude that the H3K27me3/H3K36me3 gene body chromatin signature is an informative proxy of monoallelic expression in mouse clonal B lymphoid cells and the MaGIC pipeline is up to 73% accurate for inferring MAE.

Bottom Line: Recently, we reported that a specific histone modification signature is strongly associated with MAE and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells.Our analyses reveal extensive conservation in the identity of MAE genes between the two species.By analyzing MAE chromatin signature in a large number of cell and tissue types, we show that it remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute; and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02215.

No MeSH data available.