CoChat
Sign Up
Cited by 499Neurogenesis and neuroplasticity mechanismsMicroRNA in disease regulationEpigenetics and DNA Methylation

The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.

Cross talk between microRNA and epigenetic regulation in adult neurogenesis

Open access
Szulwach, Keith E., Li, Xuekun, Smrt, Richard D., Li, Yujing, Luo, Yuping, Lin, Li, Santistevan, Nicholas J., Li, Wendi, Zhao, Xinyu, Jin, Peng·2010·Journal of Cell Biology
DOI 10.1083/jcb.200908151PMC PMC2854370
Open this paper in CoChat — free accountOpen PDF

Abstract

Both microRNAs (miRNAs) and epigenetic regulation have important functions in stem cell biology, although the interactions between these two pathways are not well understood. Here, we show that MeCP2, a DNA methyl-CpG–binding protein, can epigenetically regulate specific miRNAs in adult neural stem cells (aNSCs). MeCP2-mediated epigenetic regulation of one such miRNA, miR-137, involves coregulation by Sox2, a core transcription factor in stem cells. miR-137 modulates the proliferation and differentiation of aNSCs in vitro and in vivo. Overexpression of miR-137 promotes the proliferation of aNSCs, whereas a reduction of miR-137 enhances aNSC differentiation. We further show that miR-137 post-transcriptionally represses the expression of Ezh2, a histone methyltransferase and Polycomb group (PcG) protein. The miR-137–mediated repression of Ezh2 feeds back to chromatin, resulting in a global decrease in histone H3 trimethyl lysine 27. Coexpression of Ezh2 can rescue phenotypes associated with miR-137 overexpression. These results demonstrate that cross talk between miRNA and epigenetic regulation contributes to the modulation of adult neurogenesis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1083/jcb.200908151

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1. Identification of miRNAs with altered expression in Mecp2-deficient adult NSCs. (A) Adult NSCs cultured under proliferating conditions express Sox2 (nuclear, green) and Nestin (cytoplasmic, red), and incorporate BrdU (nuclear, red). Adult NSCs used in this study were multipotent and, when subjected to differentiation, expressed neuron-specific TuJ1 (red) and astrocyte-specific GFAP (green, DAPI is shown in blue), Bar, 50 µm. (B) Western blot showing expression of MeCP2 in WT aNSCs and the absence of MeCP2 in MeCP2-/y aNSCs (ab2828 antibody; Abcam). (C) Heat map of miRNA with a ≥2.5-fold change in expression in proliferating MeCP2-/y aNSCs. Quantities relative to WT aNSCs from each of four independent miRNA profiling experiments are shown. Relative quantity scale is shown below for reference. (D) Relative quantity of miRNA with ≥2.5-fold change in expression shown for MeCP2-/y proliferating aNSCs, calibrated to WT proliferating aNSCs. WT relative quantity = 1, mean relative quantity from three WT/MeCP2-/y pairs plus one pooled sample per genotype is plotted, with error bars representing a 95% CI. Dotted lines indicate a threshold of 2.5-fold change in expression.
Figure 1. Identification of miRNAs with altered expression in Mecp2-deficient adult NSCs. (A) Adult NSCs cultured under proliferating conditions express Sox2 (nuclear, green) and Nestin (cytoplasmic, red), and incorporate BrdU (nuclear, red). Adult NSCs used in this study were multipotent and, when subjected to differentiation, expressed neuron-specific TuJ1 (red) and astrocyte-specific GFAP (green, DAPI is shown in blue), Bar, 50 µm. (B) Western blot showing expression of MeCP2 in WT aNSCs and the absence of MeCP2 in MeCP2-/y aNSCs (ab2828 antibody; Abcam). (C) Heat map of miRNA with a ≥2.5-fold change in expression in proliferating MeCP2-/y aNSCs. Quantities relative to WT aNSCs from each of four independent miRNA profiling experiments are shown. Relative quantity scale is shown below for reference. (D) Relative quantity of miRNA with ≥2.5-fold change in expression shown for MeCP2-/y proliferating aNSCs, calibrated to WT proliferating aNSCs. WT relative quantity = 1, mean relative quantity from three WT/MeCP2-/y pairs plus one pooled sample per genotype is plotted, with error bars representing a 95% CI. Dotted lines indicate a threshold of 2.5-fold change in expression.CC BY-NC-SA · PubMed Central
Figure 2. Expression of miR-137 is epigenetically regulated by MeCP2. (A) Verification of increased expression of miR-137 in MeCP2-/y proliferating aNSCs using independent real-time PCR (n = 6, mean relative quantity ± SEM, P = 0.022). (B) Schematic of the 7 kb proximal to miR-137 on chromosome 3qG1 that were assayed in ChIP experiments. The region 2.5 kb upstream is indicated, along with a previously identified transcriptional start site that lies 2.2 kb upstream of miR-137 (Shiraki et al., 2003; Carninci et al., 2005). (C) MeCP2-specific ChIP indicates the enrichment of DNA 2.5 kb upstream of the miR-137 genomic locus in WT aNSCs, but not MeCP2-/y aNSCs. Relative enrichment is calculated relative to IgG-only nonspecific control and normalized to the directly adjacent 1.5-kb upstream region (n = 3, two-way analysis of variance [ANOVA], Bonferroni post-test; ***, P < 0.001). (D) IP of 5′-Me-C (MeDIP) showing enrichment of methylated cytosines between 4.5 and 1.5 kb upstream of miR-137, with which MeCP2 may normally bind (n = 3). (E) H3-K4-Tri-Me–specific ChIP indicates increased enrichment of sequences 2.5 kb upstream of miR-137, as well as sequences in a 1-kb region directly surrounding miR-137 in MeCP2-/y aNSCs. (F) H3-K9-Ac–specific ChIP with increased enrichment of sequences in the 1 kb surrounding miR-137 in MeCP2-/y aNSCs. In all histone ChIP experiments: n = 3, two-way ANOVA, Bonferroni post-test, quantities calculated from an input DNA-generated standard curve; **, P < 0.01; ***, P < 0.001. Quantities in IgG-only nonspecific IP control experiments in E–G are near 0. Error bars indicate mean ± SEM.
Figure 2. Expression of miR-137 is epigenetically regulated by MeCP2. (A) Verification of increased expression of miR-137 in MeCP2-/y proliferating aNSCs using independent real-time PCR (n = 6, mean relative quantity ± SEM, P = 0.022). (B) Schematic of the 7 kb proximal to miR-137 on chromosome 3qG1 that were assayed in ChIP experiments. The region 2.5 kb upstream is indicated, along with a previously identified transcriptional start site that lies 2.2 kb upstream of miR-137 (Shiraki et al., 2003; Carninci et al., 2005). (C) MeCP2-specific ChIP indicates the enrichment of DNA 2.5 kb upstream of the miR-137 genomic locus in WT aNSCs, but not MeCP2-/y aNSCs. Relative enrichment is calculated relative to IgG-only nonspecific control and normalized to the directly adjacent 1.5-kb upstream region (n = 3, two-way analysis of variance [ANOVA], Bonferroni post-test; ***, P < 0.001). (D) IP of 5′-Me-C (MeDIP) showing enrichment of methylated cytosines between 4.5 and 1.5 kb upstream of miR-137, with which MeCP2 may normally bind (n = 3). (E) H3-K4-Tri-Me–specific ChIP indicates increased enrichment of sequences 2.5 kb upstream of miR-137, as well as sequences in a 1-kb region directly surrounding miR-137 in MeCP2-/y aNSCs. (F) H3-K9-Ac–specific ChIP with increased enrichment of sequences in the 1 kb surrounding miR-137 in MeCP2-/y aNSCs. In all histone ChIP experiments: n = 3, two-way ANOVA, Bonferroni post-test, quantities calculated from an input DNA-generated standard curve; **, P < 0.01; ***, P < 0.001. Quantities in IgG-only nonspecific IP control experiments in E–G are near 0. Error bars indicate mean ± SEM.CC BY-NC-SA · PubMed Central
Figure 3. Transcriptional regulation of miR-137 involves coregulation by Sox2. (A) Schematic showing the miR-137 genomic locus and the location of a conserved Sox2 consensus-binding site within the 2.5-kb upstream region of miR-137 with which MeCP2 was also found to interact by ChIP. (B and C) Genomic structure and CpG content surrounding the miR-137 genomic locus. (B) Percentage of CG content across a 7-kb region surrounding miR-137, with a threshold indicated at 60%. (C) Ratio of observed CpG dinucleotides to the number of CpGs expected with a normal distribution across the same 7-kb region surrounding miR-137. A threshold is indicated at a ratio of 0.6 (dotted line). Data for both plots were generated using EMBOSS CpG plot with a 100-nt window size and a 1-nt window shift increment (Larsen et al., 1992). (D) Sequences 2.5 kb upstream of miR-137 enriched in a Sox2-specific ChIP relative to IgG only in WT aNSCs but not MeCP2-/y aNSCs, normalized to the directly adjacent 1.5-kb upstream region (n = 3, error bars indicate mean ± SEM, two-way ANOVA, Bonferroni post-test; ***, P < 0.001). (E) MeCP2 and Sox2 could be coimmunoprecipitated. Either MeCP2 or Sox2 was immunoprecipitated and subjected to Western blots with anti-Sox2 or anti-MeCP2 antibodies, respectively. IP beads only and IP with normal IgG were used as negative controls.
Figure 3. Transcriptional regulation of miR-137 involves coregulation by Sox2. (A) Schematic showing the miR-137 genomic locus and the location of a conserved Sox2 consensus-binding site within the 2.5-kb upstream region of miR-137 with which MeCP2 was also found to interact by ChIP. (B and C) Genomic structure and CpG content surrounding the miR-137 genomic locus. (B) Percentage of CG content across a 7-kb region surrounding miR-137, with a threshold indicated at 60%. (C) Ratio of observed CpG dinucleotides to the number of CpGs expected with a normal distribution across the same 7-kb region surrounding miR-137. A threshold is indicated at a ratio of 0.6 (dotted line). Data for both plots were generated using EMBOSS CpG plot with a 100-nt window size and a 1-nt window shift increment (Larsen et al., 1992). (D) Sequences 2.5 kb upstream of miR-137 enriched in a Sox2-specific ChIP relative to IgG only in WT aNSCs but not MeCP2-/y aNSCs, normalized to the directly adjacent 1.5-kb upstream region (n = 3, error bars indicate mean ± SEM, two-way ANOVA, Bonferroni post-test; ***, P < 0.001). (E) MeCP2 and Sox2 could be coimmunoprecipitated. Either MeCP2 or Sox2 was immunoprecipitated and subjected to Western blots with anti-Sox2 or anti-MeCP2 antibodies, respectively. IP beads only and IP with normal IgG were used as negative controls.CC BY-NC-SA · PubMed Central
Figure 4. miR-137 modulates the proliferation and differentiation of adult NSCs in vitro. (A) Cell proliferation was analyzed using BrdU pulse labeling. Quantitative analysis by stereology indicates that miR-137-overexpressing aNSCs (GFP positive) produced more BrdU+ cells, which indicates increased proliferation relative to control-treated cells (*, P = 0.0403; unpaired t test, n = 3). (B) Anti–miR-137–treated aNSCs produced fewer BrdU+ cells relative to anti–miR-control aNSCs (**, P = 0.0024; unpaired t test, n = 3). (C) Representative images of WT aNSCs infected with lentivirus expressing either sh-control or lentivirus expressing sh-miR-137, which were pulse-labeled with BrdU. Insets show 3× enlarged views of the boxed regions. Bar, 50 µm. (D) sh-miR-137–infected cells differentiated into fewer neurons compared with sh-control virus-infected cells, as determined by the percentage of TuJ1-positive cells among infected, GFP-positive cells (**, P = 0.0037; unpaired t test, n = 3). (E) Anti–miR-137 treatment reduces production of TuJ1-positive cells during differentiation (***, P < 0.0001; n = 3) (F) Among infected, GFP-positive cells, sh-miR-137–infected cells differentiated into fewer GFAP-positive cells compared with sh-control virus-infected cells (**, P = 0.0046; unpaired t test, n = 3). (G) Anti–miR-137 treatment reduces production of GFAP-positive cells during differentiation (*, P = 0.0483; n = 3). (H) Representative images of lentivirus-infected NSCs that were differentiated into Tuj1-positive neurons (red) and GFAP-positive astrocytes (blue). Bar, 50 µm. (I) Although overexpression of miR-137 leads to a decrease in NeuroD1-promoter activity relative to control treatment and as assessed by a luciferase reporter (*, P = 0.0128; unpaired t test, n ≥ 3), anti–miR-137 treatment leads to increased NeuroD1-promoter-luciferase activity (**, P = 0.0046; unpaired t test, n = 3). Control treatments are normalized to 1.0. (J) Overexpression of miR-137 leads to a decrease in GFAP promoter activity (**, P = 0.0021; unpaired t test, n = 3), whereas anti–miR-137 treatment leads to increased GFAP luciferase activity (***, P = 0.0007; unpaired t test, n = 3). Data in all panels are plotted as mean ± SEM (error bars).
Figure 4. miR-137 modulates the proliferation and differentiation of adult NSCs in vitro. (A) Cell proliferation was analyzed using BrdU pulse labeling. Quantitative analysis by stereology indicates that miR-137-overexpressing aNSCs (GFP positive) produced more BrdU+ cells, which indicates increased proliferation relative to control-treated cells (*, P = 0.0403; unpaired t test, n = 3). (B) Anti–miR-137–treated aNSCs produced fewer BrdU+ cells relative to anti–miR-control aNSCs (**, P = 0.0024; unpaired t test, n = 3). (C) Representative images of WT aNSCs infected with lentivirus expressing either sh-control or lentivirus expressing sh-miR-137, which were pulse-labeled with BrdU. Insets show 3× enlarged views of the boxed regions. Bar, 50 µm. (D) sh-miR-137–infected cells differentiated into fewer neurons compared with sh-control virus-infected cells, as determined by the percentage of TuJ1-positive cells among infected, GFP-positive cells (**, P = 0.0037; unpaired t test, n = 3). (E) Anti–miR-137 treatment reduces production of TuJ1-positive cells during differentiation (***, P < 0.0001; n = 3) (F) Among infected, GFP-positive cells, sh-miR-137–infected cells differentiated into fewer GFAP-positive cells compared with sh-control virus-infected cells (**, P = 0.0046; unpaired t test, n = 3). (G) Anti–miR-137 treatment reduces production of GFAP-positive cells during differentiation (*, P = 0.0483; n = 3). (H) Representative images of lentivirus-infected NSCs that were differentiated into Tuj1-positive neurons (red) and GFAP-positive astrocytes (blue). Bar, 50 µm. (I) Although overexpression of miR-137 leads to a decrease in NeuroD1-promoter activity relative to control treatment and as assessed by a luciferase reporter (*, P = 0.0128; unpaired t test, n ≥ 3), anti–miR-137 treatment leads to increased NeuroD1-promoter-luciferase activity (**, P = 0.0046; unpaired t test, n = 3). Control treatments are normalized to 1.0. (J) Overexpression of miR-137 leads to a decrease in GFAP promoter activity (**, P = 0.0021; unpaired t test, n = 3), whereas anti–miR-137 treatment leads to increased GFAP luciferase activity (***, P = 0.0007; unpaired t test, n = 3). Data in all panels are plotted as mean ± SEM (error bars).CC BY-NC-SA · PubMed Central
Figure 5. miR-137 modulates the proliferation and differentiation of adult NSCs in vivo. (A) A schematic diagram of the retroviral vector used for in vivo miRNA expression. (B, left) sh-miR-137–infected cells differentiated into fewer DCX+ early neurons compared with sh-control virus-infected cells (n ≥ 3; *, P < 0.05; error bars indicate mean ± SEM). (B, right) A representative confocal 3D z-stack image used for quantification of DCX+GFP+ cells. (C, left) More sh-miR-137–infected cells proliferated than control virus-infected cells (n = 3; *, P < 0.05; error bars indicate mean ± SEM). (C, right) A representative 3D z-stack image used for quantification of BrdU+GFP+ cells (Bar, 5 µm). (D) A representative image of immunohistological analysis of virus-infected endogenous aNSCs in the subgranular zone of the DG. Arrowheads indicate a cell that is positive for GFP (green), BrdU (white), and DCX (red), which suggests that this cell was proliferating during the viral grafting period and has differentiated into early neurons within 1 wk of grafting. Arrows indicate a cell that is positive for GFP and BrdU, but not for DCX, which indicates that this cell did not differentiate. Bars: (B and C) 5 µm; (D) 20 µm.
Figure 5. miR-137 modulates the proliferation and differentiation of adult NSCs in vivo. (A) A schematic diagram of the retroviral vector used for in vivo miRNA expression. (B, left) sh-miR-137–infected cells differentiated into fewer DCX+ early neurons compared with sh-control virus-infected cells (n ≥ 3; *, P < 0.05; error bars indicate mean ± SEM). (B, right) A representative confocal 3D z-stack image used for quantification of DCX+GFP+ cells. (C, left) More sh-miR-137–infected cells proliferated than control virus-infected cells (n = 3; *, P < 0.05; error bars indicate mean ± SEM). (C, right) A representative 3D z-stack image used for quantification of BrdU+GFP+ cells (Bar, 5 µm). (D) A representative image of immunohistological analysis of virus-infected endogenous aNSCs in the subgranular zone of the DG. Arrowheads indicate a cell that is positive for GFP (green), BrdU (white), and DCX (red), which suggests that this cell was proliferating during the viral grafting period and has differentiated into early neurons within 1 wk of grafting. Arrows indicate a cell that is positive for GFP and BrdU, but not for DCX, which indicates that this cell did not differentiate. Bars: (B and C) 5 µm; (D) 20 µm.CC BY-NC-SA · PubMed Central
Figure 6. Ezh2 is a functional target of miR-137. (A) Primary screen of predicted miR-137 targets in HEK293FT cells. 3′ UTR–dependent luciferase assays were performed using both sh-control and sh-miR-137 for each of 15 predicted miR-137 targets. For each 3′ UTR, luciferase expression was normalized (hRluc/hluc) to 1 for the sh-control control treatment, as indicated by the dotted line. The effect of sh-miR-137 was then calculated relative to sh-control (sh-miR-137/sh-control). For all experiments, n ≥ 3, error bars indicate mean ± SEM. (B) Coexpression of Ezh2 rescued the decreased NeuroD1-luciferase expression caused by the overexpression of miR-137 in aNSCs. NeuroD1 promoter luciferase activity was normalized to coelectroporated E1a-Renilla luciferase activity (n ≥ 3 for all experiments, one-way ANOVA with Bonferroni post-test; **, P < 0.01; ns, P > 0.05). (C) Coexpression of Ezh2 rescued the decreased neuronal differentiation caused by the overexpression of miR-137 in aNSCs, as determined by the percentage of TuJ1-positive cells among infected, GFP-positive cells (unpaired t test, n = 3; *, P = 0.0016). (D) The miR-137 7mer-1A target site in the Ezh2 3′ UTR as predicted by TargetScan. (E) Ezh2-3′ UTR–dependent expression of a luciferase reporter gene was suppressed by miR-137 in HEK293FT cells. MiR-137–mediated suppression of luciferase was specific, as deletion of the miR-137 target site in the Ezh2 3′ UTR abolished repression by miR-137. Renilla luciferase-Ezh2–3′ UTR expression was normalized to firefly luciferase (n = 6 for HEK293FT cells, unpaired t test; **, P < 0.05).
Figure 6. Ezh2 is a functional target of miR-137. (A) Primary screen of predicted miR-137 targets in HEK293FT cells. 3′ UTR–dependent luciferase assays were performed using both sh-control and sh-miR-137 for each of 15 predicted miR-137 targets. For each 3′ UTR, luciferase expression was normalized (hRluc/hluc) to 1 for the sh-control control treatment, as indicated by the dotted line. The effect of sh-miR-137 was then calculated relative to sh-control (sh-miR-137/sh-control). For all experiments, n ≥ 3, error bars indicate mean ± SEM. (B) Coexpression of Ezh2 rescued the decreased NeuroD1-luciferase expression caused by the overexpression of miR-137 in aNSCs. NeuroD1 promoter luciferase activity was normalized to coelectroporated E1a-Renilla luciferase activity (n ≥ 3 for all experiments, one-way ANOVA with Bonferroni post-test; **, P < 0.01; ns, P > 0.05). (C) Coexpression of Ezh2 rescued the decreased neuronal differentiation caused by the overexpression of miR-137 in aNSCs, as determined by the percentage of TuJ1-positive cells among infected, GFP-positive cells (unpaired t test, n = 3; *, P = 0.0016). (D) The miR-137 7mer-1A target site in the Ezh2 3′ UTR as predicted by TargetScan. (E) Ezh2-3′ UTR–dependent expression of a luciferase reporter gene was suppressed by miR-137 in HEK293FT cells. MiR-137–mediated suppression of luciferase was specific, as deletion of the miR-137 target site in the Ezh2 3′ UTR abolished repression by miR-137. Renilla luciferase-Ezh2–3′ UTR expression was normalized to firefly luciferase (n = 6 for HEK293FT cells, unpaired t test; **, P < 0.05).CC BY-NC-SA · PubMed Central
Figure 7. Overexpression of miR-137 suppresses the expression of Ezh2 post-transcriptionally and results in an overall reduction in H3K27-TriMe. (A) Overexpression of miR-137 in WT aNSCs led to the reduction of endogenous Ezh2 protein expression (top, n = 4; *, P = 0.0366) without a proportional reduction in Ezh2 mRNA (bottom, n = 3, error bars indicate the mean with a 95% CI). (B) Loss of MeCP2 in aNSCs led to a similar reduction in endogenous Ezh2 protein expression (top, n = 4; *, P = 0.0417) without a proportional reduction in Ezh2 mRNA (bottom, n = 3, error bars indicate the mean with a 95% CI). (C) Overexpression miR-137 resulted in a reduction in H3K27-TriMe relative to histone H4 (*, P = 0.0379; n ≥ 3, unpaired t test). (D) H3K27-TriMe is also reduced relative to histone H4 in MeCP2-/y aNSCs (*, P = 0.0367; n ≥ 3, unpaired t test). (E) Model for the cross talk between MeCP2, miR-137, and Ezh2 in modulating adult neurogenesis. MeCP2 along with Sox2 mediates the epigenetic regulation of miR-137 in aNSCs, where increased expression of miR-137 promotes aNSC proliferation and inhibits aNSC differentiation, whereas decreased expression of miR-137 promotes differentiation of aNSCs. One target gene involved in this process is Ezh2. The miR-137–mediated suppression of Ezh2 feeds back to chromatin by decreasing global H3K27-TriMe. Error bars indicate mean ± SEM.
Figure 7. Overexpression of miR-137 suppresses the expression of Ezh2 post-transcriptionally and results in an overall reduction in H3K27-TriMe. (A) Overexpression of miR-137 in WT aNSCs led to the reduction of endogenous Ezh2 protein expression (top, n = 4; *, P = 0.0366) without a proportional reduction in Ezh2 mRNA (bottom, n = 3, error bars indicate the mean with a 95% CI). (B) Loss of MeCP2 in aNSCs led to a similar reduction in endogenous Ezh2 protein expression (top, n = 4; *, P = 0.0417) without a proportional reduction in Ezh2 mRNA (bottom, n = 3, error bars indicate the mean with a 95% CI). (C) Overexpression miR-137 resulted in a reduction in H3K27-TriMe relative to histone H4 (*, P = 0.0379; n ≥ 3, unpaired t test). (D) H3K27-TriMe is also reduced relative to histone H4 in MeCP2-/y aNSCs (*, P = 0.0367; n ≥ 3, unpaired t test). (E) Model for the cross talk between MeCP2, miR-137, and Ezh2 in modulating adult neurogenesis. MeCP2 along with Sox2 mediates the epigenetic regulation of miR-137 in aNSCs, where increased expression of miR-137 promotes aNSC proliferation and inhibits aNSC differentiation, whereas decreased expression of miR-137 promotes differentiation of aNSCs. One target gene involved in this process is Ezh2. The miR-137–mediated suppression of Ezh2 feeds back to chromatin by decreasing global H3K27-TriMe. Error bars indicate mean ± SEM.CC BY-NC-SA · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 69 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Szulwach, K. E., Li, X., Smrt, R. D., Li, Y., Luo, Y., Lin, L., Santistevan, N. J., Li, W., Zhao, X., & Jin, P.
Affiliations
  • Emory University (US)
  • University of New Mexico (US)
  • Department of Human Genetics 1 and 2
Corresponding author
  • Zhao, Xinyu
  • Jin, Peng
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2010-04-05
Volume
189
Issue
1
Pages
127-141
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200908151
PMC
PMC2854370
OpenAlex
W2146997290
Cited by
493
References
69
Citations by year
2026: 5 · 2025: 12 · 2024: 28 · 2023: 13 · 2022: 22 · 2021: 31 · 2020: 13 · 2019: 28 · 2018: 22 · 2017: 34 · 2016: 43 · 2015: 45 · 2014: 55 · 2013: 43 · 2012: 48
FWCI
14.26
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Autism Speaks
  • International Rett Syndrome Foundation
  • National Institutes of Health
  • National Institute on Aging (P50AG025688)
  • National Institute of Mental Health (R01MH078972, MH078972, R56MH076090, MH080434, R01MH076090, MH076090, R01MH080434)
  • National Institute of General Medical Sciences (T34GM008751)
  • National Institute of Neurological Disorders and Stroke (NS051630, R01NS051630)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
microRNA, epigenetic regulation, adult neurogenesis, adult neural stem cells, MeCP2, miR-137, SOX2, EZH2, Polycomb group proteins, H3K27me3, DNA methylation, stem cell proliferation, stem cell differentiation, post-transcriptional regulation
MeSH terms
Enhancer of Zeste Homolog 2 Protein, Animals, Chromatin, Mice, Transgenic, Histone-Lysine N-Methyltransferase, Repressor Proteins, Stem Cells, MicroRNAs, Epigenesis, Genetic, Mice, Methyl-CpG-Binding Protein 2, Neurogenesis, Polycomb-Group Proteins, Polycomb Repressive Complex 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review