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Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1

View Article: PubMed Central - PubMed

ABSTRACT

Neural cell fate acquisition is mediated by transcription factors expressed in nascent neuroectoderm, including Geminin and members of the Zic transcription factor family. However, regulatory networks through which this occurs are not well defined. Here, we identified Geminin-associated chromatin locations in embryonic stem cells and Geminin- and Zic1-associated locations during neural fate acquisition at a genome-wide level. We determined how Geminin deficiency affected histone acetylation at gene promoters during this process. We integrated these data to demonstrate that Geminin associates with and promotes histone acetylation at neurodevelopmental genes, while Geminin and Zic1 bind a shared gene subset. Geminin- and Zic1-associated genes exhibit embryonic nervous system-enriched expression and encode other regulators of neural development. Both Geminin and Zic1-associated peaks are enriched for Zic1 consensus binding motifs, while Zic1-bound peaks are also enriched for Sox3 motifs, suggesting co-regulatory potential. Accordingly, we found that Geminin and Zic1 could cooperatively activate the expression of several shared targets encoding transcription factors that control neurogenesis, neural plate patterning, and neuronal differentiation. We used these data to construct gene regulatory networks underlying neural fate acquisition. Establishment of this molecular program in nascent neuroectoderm directly links early neural cell fate acquisition with regulatory control of later neurodevelopment.

No MeSH data available.


Comparison of Gmnn-associated and Zic1-associated genes in NE.(A) A subset of genes is associated with both Gmnn and Zic1. p-value (Chi-square test with Yates’ correction) <2.2 × 10−16. (B) z-scores for enrichment of expression in ES versus CNS tissues for all Zic and/or Gmnn associated genes. (C) GO enrichment analysis for associated genes with increased versus decreased expression in embryonic CNS, relative to ES cells. (D) Comparison of all Gmnn or Zic1 associated genes, subsets that undergo Gmnn-dependent acetylation, and transcription factors, with their relative enrichment of expression in embryonic CNS tissues.
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f6: Comparison of Gmnn-associated and Zic1-associated genes in NE.(A) A subset of genes is associated with both Gmnn and Zic1. p-value (Chi-square test with Yates’ correction) <2.2 × 10−16. (B) z-scores for enrichment of expression in ES versus CNS tissues for all Zic and/or Gmnn associated genes. (C) GO enrichment analysis for associated genes with increased versus decreased expression in embryonic CNS, relative to ES cells. (D) Comparison of all Gmnn or Zic1 associated genes, subsets that undergo Gmnn-dependent acetylation, and transcription factors, with their relative enrichment of expression in embryonic CNS tissues.

Mentions: We also compared Geminin- and Zic1-associated genes defined by ChIP-seq in NE. 3291 Zic1-associated peaks were defined; these corresponded to the nearest transcription start sites of 2283 genes, including 628 genes that also have Gmnn associated peaks in NE (Fig. 6A). Like the Gmnn-associated genes, the Zic1-associated gene set exhibited embryonic CNS-enriched expression (Fig. 6B). Gmnn and Zic1 association occurred through intersecting peak locations on the genome at some of these genes (201 intersecting peaks of Gmnn-Zic1 association), suggesting the potential for Gmnn and Zic1 cooperative activity in regulating their expression.


Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1
Comparison of Gmnn-associated and Zic1-associated genes in NE.(A) A subset of genes is associated with both Gmnn and Zic1. p-value (Chi-square test with Yates’ correction) <2.2 × 10−16. (B) z-scores for enrichment of expression in ES versus CNS tissues for all Zic and/or Gmnn associated genes. (C) GO enrichment analysis for associated genes with increased versus decreased expression in embryonic CNS, relative to ES cells. (D) Comparison of all Gmnn or Zic1 associated genes, subsets that undergo Gmnn-dependent acetylation, and transcription factors, with their relative enrichment of expression in embryonic CNS tissues.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121602&req=5

f6: Comparison of Gmnn-associated and Zic1-associated genes in NE.(A) A subset of genes is associated with both Gmnn and Zic1. p-value (Chi-square test with Yates’ correction) <2.2 × 10−16. (B) z-scores for enrichment of expression in ES versus CNS tissues for all Zic and/or Gmnn associated genes. (C) GO enrichment analysis for associated genes with increased versus decreased expression in embryonic CNS, relative to ES cells. (D) Comparison of all Gmnn or Zic1 associated genes, subsets that undergo Gmnn-dependent acetylation, and transcription factors, with their relative enrichment of expression in embryonic CNS tissues.
Mentions: We also compared Geminin- and Zic1-associated genes defined by ChIP-seq in NE. 3291 Zic1-associated peaks were defined; these corresponded to the nearest transcription start sites of 2283 genes, including 628 genes that also have Gmnn associated peaks in NE (Fig. 6A). Like the Gmnn-associated genes, the Zic1-associated gene set exhibited embryonic CNS-enriched expression (Fig. 6B). Gmnn and Zic1 association occurred through intersecting peak locations on the genome at some of these genes (201 intersecting peaks of Gmnn-Zic1 association), suggesting the potential for Gmnn and Zic1 cooperative activity in regulating their expression.

View Article: PubMed Central - PubMed

ABSTRACT

Neural cell fate acquisition is mediated by transcription factors expressed in nascent neuroectoderm, including Geminin and members of the Zic transcription factor family. However, regulatory networks through which this occurs are not well defined. Here, we identified Geminin-associated chromatin locations in embryonic stem cells and Geminin- and Zic1-associated locations during neural fate acquisition at a genome-wide level. We determined how Geminin deficiency affected histone acetylation at gene promoters during this process. We integrated these data to demonstrate that Geminin associates with and promotes histone acetylation at neurodevelopmental genes, while Geminin and Zic1 bind a shared gene subset. Geminin- and Zic1-associated genes exhibit embryonic nervous system-enriched expression and encode other regulators of neural development. Both Geminin and Zic1-associated peaks are enriched for Zic1 consensus binding motifs, while Zic1-bound peaks are also enriched for Sox3 motifs, suggesting co-regulatory potential. Accordingly, we found that Geminin and Zic1 could cooperatively activate the expression of several shared targets encoding transcription factors that control neurogenesis, neural plate patterning, and neuronal differentiation. We used these data to construct gene regulatory networks underlying neural fate acquisition. Establishment of this molecular program in nascent neuroectoderm directly links early neural cell fate acquisition with regulatory control of later neurodevelopment.

No MeSH data available.