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Molecular targets of chromatin repressive mark H3K9me3 in primate progenitor cells within adult neurogenic niches.

Foret MR, Sandstrom RS, Rhodes CT, Wang Y, Berger MS, Lin CH - Front Genet (2014)

Bottom Line: Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric heterochromatin and important in genomic stability.Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human.Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Texas at San Antonio San Antonio, TX, USA.

ABSTRACT
Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3) is enriched in an adult neural stem cell niche- the subventricular zone (SVZ) on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing) and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.

No MeSH data available.


H3K9me3 distribution in mouse SVZ. (A) Coronal cross-section view of mouse forebrain, box indicates location of SVZ. (B) H3K9me3 staining pattern in SVZ cells (100X). (C–E) Double labeling of H3K9me3 (red) and SVZ cell-type specific markers: (C) NSC marker—GFAP; (D) Active NSC cell marker—Vimentin; (E) Neuroblast marker—PSA-NCAM. (F) Small population of H3K9me3-positive cells is colocalized with Mash1. (G,H) Small population of EdU+ cells is colocalized with H3K9me3. (I) Scheme displays cell type specific markers at different neural progenitor stages. LV, lateral ventricle; Images represent 12 μm coronal sections at 40X magnification; Scale bar = 20 μm.
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Figure 1: H3K9me3 distribution in mouse SVZ. (A) Coronal cross-section view of mouse forebrain, box indicates location of SVZ. (B) H3K9me3 staining pattern in SVZ cells (100X). (C–E) Double labeling of H3K9me3 (red) and SVZ cell-type specific markers: (C) NSC marker—GFAP; (D) Active NSC cell marker—Vimentin; (E) Neuroblast marker—PSA-NCAM. (F) Small population of H3K9me3-positive cells is colocalized with Mash1. (G,H) Small population of EdU+ cells is colocalized with H3K9me3. (I) Scheme displays cell type specific markers at different neural progenitor stages. LV, lateral ventricle; Images represent 12 μm coronal sections at 40X magnification; Scale bar = 20 μm.

Mentions: Using co-immunostaining with antibodies specific for H3K9me3 (a pericentric chromatin staining pattern, Figure 1B) and cell type specific markers in the SVZ (Figure 1I) for the gross anatomy of 8-week (P56) old adult mouse brain (Figure 1A), we found that H3K9me3-positive cells are co-localized with GFAP which labels quiescent and active NSCs (Figure 1C), Vimentin positive active NSC (Figure 1D), and PSA-NCAM positive neuroblast populations as well (Figure 1E). As Mash1 is commonly used in the mouse to denote cells as “transient amplifying cells,” we applied co-immunostaining of Mash1 and H3K9me3 in the mouse SVZ, and found colocalization of H3K9me3 and Mash1 (Figure 1F). We then performed a 2 h EdU administration in mice to label quickly dividing transit-amplifying cells and neuroblasts, and found colocalization of EdU and H3K9me3 (Figures 1G,H). These results show that H3K9me3 is present in undifferentiated SVZ cells within rodent brain.


Molecular targets of chromatin repressive mark H3K9me3 in primate progenitor cells within adult neurogenic niches.

Foret MR, Sandstrom RS, Rhodes CT, Wang Y, Berger MS, Lin CH - Front Genet (2014)

H3K9me3 distribution in mouse SVZ. (A) Coronal cross-section view of mouse forebrain, box indicates location of SVZ. (B) H3K9me3 staining pattern in SVZ cells (100X). (C–E) Double labeling of H3K9me3 (red) and SVZ cell-type specific markers: (C) NSC marker—GFAP; (D) Active NSC cell marker—Vimentin; (E) Neuroblast marker—PSA-NCAM. (F) Small population of H3K9me3-positive cells is colocalized with Mash1. (G,H) Small population of EdU+ cells is colocalized with H3K9me3. (I) Scheme displays cell type specific markers at different neural progenitor stages. LV, lateral ventricle; Images represent 12 μm coronal sections at 40X magnification; Scale bar = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4115620&req=5

Figure 1: H3K9me3 distribution in mouse SVZ. (A) Coronal cross-section view of mouse forebrain, box indicates location of SVZ. (B) H3K9me3 staining pattern in SVZ cells (100X). (C–E) Double labeling of H3K9me3 (red) and SVZ cell-type specific markers: (C) NSC marker—GFAP; (D) Active NSC cell marker—Vimentin; (E) Neuroblast marker—PSA-NCAM. (F) Small population of H3K9me3-positive cells is colocalized with Mash1. (G,H) Small population of EdU+ cells is colocalized with H3K9me3. (I) Scheme displays cell type specific markers at different neural progenitor stages. LV, lateral ventricle; Images represent 12 μm coronal sections at 40X magnification; Scale bar = 20 μm.
Mentions: Using co-immunostaining with antibodies specific for H3K9me3 (a pericentric chromatin staining pattern, Figure 1B) and cell type specific markers in the SVZ (Figure 1I) for the gross anatomy of 8-week (P56) old adult mouse brain (Figure 1A), we found that H3K9me3-positive cells are co-localized with GFAP which labels quiescent and active NSCs (Figure 1C), Vimentin positive active NSC (Figure 1D), and PSA-NCAM positive neuroblast populations as well (Figure 1E). As Mash1 is commonly used in the mouse to denote cells as “transient amplifying cells,” we applied co-immunostaining of Mash1 and H3K9me3 in the mouse SVZ, and found colocalization of H3K9me3 and Mash1 (Figure 1F). We then performed a 2 h EdU administration in mice to label quickly dividing transit-amplifying cells and neuroblasts, and found colocalization of EdU and H3K9me3 (Figures 1G,H). These results show that H3K9me3 is present in undifferentiated SVZ cells within rodent brain.

Bottom Line: Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric heterochromatin and important in genomic stability.Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human.Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Texas at San Antonio San Antonio, TX, USA.

ABSTRACT
Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3) is enriched in an adult neural stem cell niche- the subventricular zone (SVZ) on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing) and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.

No MeSH data available.