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Astrocyte-specific genes are generally demethylated in neural precursor cells prior to astrocytic differentiation.

Hatada I, Namihira M, Morita S, Kimura M, Horii T, Nakashima K - PLoS ONE (2008)

Bottom Line: This differentiation-potential switch could be explained by epigenetic changes, since the promoters of astrocyte-specific marker genes, glial fibrillary acidic protein (Gfap) and S100beta, have been shown to become demethylated in late-stage NPCs prior to the onset of astrocyte differentiation; however, whether demethylation occurs generally in other astrocyctic genes remains unknown.Although these genes are already demethylated in late-stage NPCs, they are not expressed until cells differentiate into astrocytes.Thus, late-stage NPCs have epigenetic potential which can be realized in their expression after astrocyte differentiation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. ihatada@showa.gunma-u.ac.jp

ABSTRACT
Epigenetic changes are thought to lead to alterations in the property of cells, such as differentiation potential. Neural precursor cells (NPCs) differentiate only into neurons in the midgestational brain, yet they become able to generate astrocytes in the late stage of development. This differentiation-potential switch could be explained by epigenetic changes, since the promoters of astrocyte-specific marker genes, glial fibrillary acidic protein (Gfap) and S100beta, have been shown to become demethylated in late-stage NPCs prior to the onset of astrocyte differentiation; however, whether demethylation occurs generally in other astrocyctic genes remains unknown. Here we analyzed DNA methylation changes in mouse NPCs between the mid-(E11.5) and late (E14.5) stage of development by a genome-wide DNA methylation profiling method using microarrays and found that many astrocytic genes are demethylated in late-stage NPCs, enabling the cell to become competent to express these genes. Although these genes are already demethylated in late-stage NPCs, they are not expressed until cells differentiate into astrocytes. Thus, late-stage NPCs have epigenetic potential which can be realized in their expression after astrocyte differentiation.

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DNA methylation and expression.(A) All probes are grouped by their average methylation ratios and their expression levels are indicated as average±standard error of mean. Expression levels are described as normalized values in log scale. (B) Expression levels of hypermethylated (red) and hypomethylated (blue) genes in astrocytes. Expression levels are indicated as average±standard error of mean.
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pone-0003189-g007: DNA methylation and expression.(A) All probes are grouped by their average methylation ratios and their expression levels are indicated as average±standard error of mean. Expression levels are described as normalized values in log scale. (B) Expression levels of hypermethylated (red) and hypomethylated (blue) genes in astrocytes. Expression levels are indicated as average±standard error of mean.

Mentions: To analyze the relation between the DNA methylation and the expression of genes, we plotted the methylation ratio calculated by MIAMI and the expression level calculated by expression microarray analysis for all genes examined (Fig. 7A). As expected, the methylation ratio is inversely correlated to the expression level. Next we analyzed the average expression levels of hypermethylated and hypomethylated genes in astrocytes compared to E11.5 NPCs (Fig. 7B). Although there are some exceptions, we found the average expression levels of hypermethylated genes were low and those of hypomethylated genes were high in astrocytes. One of the reasons which could explain the existence of exceptions is the wide distribution of the probes (between −8000 to +2000 bases from the transcription start sites). Interestingly, the expression levels of hypomethylated genes were low in E14.5 NPCs compared to ones in astrocytes. This again indicates activation of expression appears after differentiation into astrocytes.


Astrocyte-specific genes are generally demethylated in neural precursor cells prior to astrocytic differentiation.

Hatada I, Namihira M, Morita S, Kimura M, Horii T, Nakashima K - PLoS ONE (2008)

DNA methylation and expression.(A) All probes are grouped by their average methylation ratios and their expression levels are indicated as average±standard error of mean. Expression levels are described as normalized values in log scale. (B) Expression levels of hypermethylated (red) and hypomethylated (blue) genes in astrocytes. Expression levels are indicated as average±standard error of mean.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2527128&req=5

pone-0003189-g007: DNA methylation and expression.(A) All probes are grouped by their average methylation ratios and their expression levels are indicated as average±standard error of mean. Expression levels are described as normalized values in log scale. (B) Expression levels of hypermethylated (red) and hypomethylated (blue) genes in astrocytes. Expression levels are indicated as average±standard error of mean.
Mentions: To analyze the relation between the DNA methylation and the expression of genes, we plotted the methylation ratio calculated by MIAMI and the expression level calculated by expression microarray analysis for all genes examined (Fig. 7A). As expected, the methylation ratio is inversely correlated to the expression level. Next we analyzed the average expression levels of hypermethylated and hypomethylated genes in astrocytes compared to E11.5 NPCs (Fig. 7B). Although there are some exceptions, we found the average expression levels of hypermethylated genes were low and those of hypomethylated genes were high in astrocytes. One of the reasons which could explain the existence of exceptions is the wide distribution of the probes (between −8000 to +2000 bases from the transcription start sites). Interestingly, the expression levels of hypomethylated genes were low in E14.5 NPCs compared to ones in astrocytes. This again indicates activation of expression appears after differentiation into astrocytes.

Bottom Line: This differentiation-potential switch could be explained by epigenetic changes, since the promoters of astrocyte-specific marker genes, glial fibrillary acidic protein (Gfap) and S100beta, have been shown to become demethylated in late-stage NPCs prior to the onset of astrocyte differentiation; however, whether demethylation occurs generally in other astrocyctic genes remains unknown.Although these genes are already demethylated in late-stage NPCs, they are not expressed until cells differentiate into astrocytes.Thus, late-stage NPCs have epigenetic potential which can be realized in their expression after astrocyte differentiation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. ihatada@showa.gunma-u.ac.jp

ABSTRACT
Epigenetic changes are thought to lead to alterations in the property of cells, such as differentiation potential. Neural precursor cells (NPCs) differentiate only into neurons in the midgestational brain, yet they become able to generate astrocytes in the late stage of development. This differentiation-potential switch could be explained by epigenetic changes, since the promoters of astrocyte-specific marker genes, glial fibrillary acidic protein (Gfap) and S100beta, have been shown to become demethylated in late-stage NPCs prior to the onset of astrocyte differentiation; however, whether demethylation occurs generally in other astrocyctic genes remains unknown. Here we analyzed DNA methylation changes in mouse NPCs between the mid-(E11.5) and late (E14.5) stage of development by a genome-wide DNA methylation profiling method using microarrays and found that many astrocytic genes are demethylated in late-stage NPCs, enabling the cell to become competent to express these genes. Although these genes are already demethylated in late-stage NPCs, they are not expressed until cells differentiate into astrocytes. Thus, late-stage NPCs have epigenetic potential which can be realized in their expression after astrocyte differentiation.

Show MeSH