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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.


Comparison of mosaic monoallelic expression (MAE) chromatin signature profiles across tissues and cell types in mouse. (A) Schematic showing the hypothetical clustering of cell types (represented by different shapes) based on similar MAE state for a particular gene, in the case where MAE is stable throughout differentiation, and in the case where it is not. (B) Comparison of MAE profiles inferred from chromatin signature across analyzed tissues and cell types. Similarity scores were calculated for each pairwise comparison using only genes informative in both samples (similarity score scale at the bottom). Average-linkage clustering was performed using Gower’s distance (see the section Materials and Methods). Sample lineages are reflected in the color of the sample name, as follows: endodermic (yellow), ectodermic (cyan), lymphoid (purple), myeloid (red), other mesodermic (orange), and embryonic stem cells (black). The expected clustering of these lineages according to their embryonic origin is also shown (bottom). Laboratories that generated the ChIP-Seq datasets are indicated in parenthesis: ENCODE/LICR (EL), ENCODE/PSU (EP), Bernstein (BB), ENCODE/Caltech (EC), Schübeler (DS), and this work (AG). (C) Proportion of MAE genes inferred from chromatin signature among cell-type specific and ubiquitously expressed genes. Genes were grouped by the number of tissues where they are expressed. Then, in each bin, the proportion of MAE genes was calculated for each tissue and plotted individually (circles) and overall (Tukey boxplot).
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fig3: Comparison of mosaic monoallelic expression (MAE) chromatin signature profiles across tissues and cell types in mouse. (A) Schematic showing the hypothetical clustering of cell types (represented by different shapes) based on similar MAE state for a particular gene, in the case where MAE is stable throughout differentiation, and in the case where it is not. (B) Comparison of MAE profiles inferred from chromatin signature across analyzed tissues and cell types. Similarity scores were calculated for each pairwise comparison using only genes informative in both samples (similarity score scale at the bottom). Average-linkage clustering was performed using Gower’s distance (see the section Materials and Methods). Sample lineages are reflected in the color of the sample name, as follows: endodermic (yellow), ectodermic (cyan), lymphoid (purple), myeloid (red), other mesodermic (orange), and embryonic stem cells (black). The expected clustering of these lineages according to their embryonic origin is also shown (bottom). Laboratories that generated the ChIP-Seq datasets are indicated in parenthesis: ENCODE/LICR (EL), ENCODE/PSU (EP), Bernstein (BB), ENCODE/Caltech (EC), Schübeler (DS), and this work (AG). (C) Proportion of MAE genes inferred from chromatin signature among cell-type specific and ubiquitously expressed genes. Genes were grouped by the number of tissues where they are expressed. Then, in each bin, the proportion of MAE genes was calculated for each tissue and plotted individually (circles) and overall (Tukey boxplot).

Mentions: We reasoned that if, once established in progenitor cells, MAE is stably maintained during differentiation, then cell types originating from the same progenitors should have more similar MAE profiles compared with each other than compared with cell types originating from different progenitors. Clustering based on the similarity of MAE profiles should, therefore, recapitulate embryonic lineage. Conversely, if genes that are MAE in progenitors frequently become BAE upon differentiation, then there should not be a strong relationship between MAE profile and embryonic lineage (Figure 3A).


Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.

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

Comparison of mosaic monoallelic expression (MAE) chromatin signature profiles across tissues and cell types in mouse. (A) Schematic showing the hypothetical clustering of cell types (represented by different shapes) based on similar MAE state for a particular gene, in the case where MAE is stable throughout differentiation, and in the case where it is not. (B) Comparison of MAE profiles inferred from chromatin signature across analyzed tissues and cell types. Similarity scores were calculated for each pairwise comparison using only genes informative in both samples (similarity score scale at the bottom). Average-linkage clustering was performed using Gower’s distance (see the section Materials and Methods). Sample lineages are reflected in the color of the sample name, as follows: endodermic (yellow), ectodermic (cyan), lymphoid (purple), myeloid (red), other mesodermic (orange), and embryonic stem cells (black). The expected clustering of these lineages according to their embryonic origin is also shown (bottom). Laboratories that generated the ChIP-Seq datasets are indicated in parenthesis: ENCODE/LICR (EL), ENCODE/PSU (EP), Bernstein (BB), ENCODE/Caltech (EC), Schübeler (DS), and this work (AG). (C) Proportion of MAE genes inferred from chromatin signature among cell-type specific and ubiquitously expressed genes. Genes were grouped by the number of tissues where they are expressed. Then, in each bin, the proportion of MAE genes was calculated for each tissue and plotted individually (circles) and overall (Tukey boxplot).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Comparison of mosaic monoallelic expression (MAE) chromatin signature profiles across tissues and cell types in mouse. (A) Schematic showing the hypothetical clustering of cell types (represented by different shapes) based on similar MAE state for a particular gene, in the case where MAE is stable throughout differentiation, and in the case where it is not. (B) Comparison of MAE profiles inferred from chromatin signature across analyzed tissues and cell types. Similarity scores were calculated for each pairwise comparison using only genes informative in both samples (similarity score scale at the bottom). Average-linkage clustering was performed using Gower’s distance (see the section Materials and Methods). Sample lineages are reflected in the color of the sample name, as follows: endodermic (yellow), ectodermic (cyan), lymphoid (purple), myeloid (red), other mesodermic (orange), and embryonic stem cells (black). The expected clustering of these lineages according to their embryonic origin is also shown (bottom). Laboratories that generated the ChIP-Seq datasets are indicated in parenthesis: ENCODE/LICR (EL), ENCODE/PSU (EP), Bernstein (BB), ENCODE/Caltech (EC), Schübeler (DS), and this work (AG). (C) Proportion of MAE genes inferred from chromatin signature among cell-type specific and ubiquitously expressed genes. Genes were grouped by the number of tissues where they are expressed. Then, in each bin, the proportion of MAE genes was calculated for each tissue and plotted individually (circles) and overall (Tukey boxplot).
Mentions: We reasoned that if, once established in progenitor cells, MAE is stably maintained during differentiation, then cell types originating from the same progenitors should have more similar MAE profiles compared with each other than compared with cell types originating from different progenitors. Clustering based on the similarity of MAE profiles should, therefore, recapitulate embryonic lineage. Conversely, if genes that are MAE in progenitors frequently become BAE upon differentiation, then there should not be a strong relationship between MAE profile and embryonic lineage (Figure 3A).

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.