Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF
Abstract Background The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases. Methods...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Molecular Autism |
| Online Access: | https://doi.org/10.1186/s13229-022-00502-9 |
| _version_ | 1818553398570516480 |
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| author | Xiaoyun Sun Linxi Cheng Yuhua Sun |
| author_facet | Xiaoyun Sun Linxi Cheng Yuhua Sun |
| author_sort | Xiaoyun Sun |
| collection | DOAJ |
| description | Abstract Background The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases. Methods We generated Pogz−/− ESCs and directed ESC differentiation toward a neural fate. We performed biochemistry, ChIP-seq, ATAC-seq, and bioinformatics analyses to understand the role of POGZ. Results We show that POGZ is required for the maintenance of ESC identity and the up-regulation of neural genes during ESC differentiation toward a neural fate. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions. POGZ functions as both a transcriptional activator and repressor, and its loss leads to deregulation of differentiation genes, including neural genes. POGZ physically associates with the SWI-SNF (esBAF) chromatin remodeler complex, and together they modulate enhancer activities via epigenetic modifications such as chromatin remodeling and histone modification. During ESC neural induction, POGZ-mediated recruitment of esBAF/BRG1 and H3K27ac are important for proper expression of neural progenitor genes. Limitations The genotype and allele relevant to human neurodevelopmental disorders is heterozygous loss of function. This work is designed to study the effects of loss of POGZ function on ESCs and during ESC neural induction. Also, this work lacks of in vivo validation using animal models. Conclusions The data suggest that POGZ is both a transcription factor and a genome regulator, and its loss leads to defects in neural induction and neurogenesis. |
| first_indexed | 2024-12-12T09:25:19Z |
| format | Article |
| id | doaj.art-e918f593efae475993d3a12c618de020 |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-12-12T09:25:19Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-e918f593efae475993d3a12c618de0202022-12-22T00:29:03ZengBMCMolecular Autism2040-23922022-06-0113111810.1186/s13229-022-00502-9Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAFXiaoyun Sun0Linxi Cheng1Yuhua Sun2Institute of Hydrobiology, Chinese Academy of SciencesInstitute of Hydrobiology, Chinese Academy of SciencesInstitute of Hydrobiology, Chinese Academy of SciencesAbstract Background The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases. Methods We generated Pogz−/− ESCs and directed ESC differentiation toward a neural fate. We performed biochemistry, ChIP-seq, ATAC-seq, and bioinformatics analyses to understand the role of POGZ. Results We show that POGZ is required for the maintenance of ESC identity and the up-regulation of neural genes during ESC differentiation toward a neural fate. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions. POGZ functions as both a transcriptional activator and repressor, and its loss leads to deregulation of differentiation genes, including neural genes. POGZ physically associates with the SWI-SNF (esBAF) chromatin remodeler complex, and together they modulate enhancer activities via epigenetic modifications such as chromatin remodeling and histone modification. During ESC neural induction, POGZ-mediated recruitment of esBAF/BRG1 and H3K27ac are important for proper expression of neural progenitor genes. Limitations The genotype and allele relevant to human neurodevelopmental disorders is heterozygous loss of function. This work is designed to study the effects of loss of POGZ function on ESCs and during ESC neural induction. Also, this work lacks of in vivo validation using animal models. Conclusions The data suggest that POGZ is both a transcription factor and a genome regulator, and its loss leads to defects in neural induction and neurogenesis.https://doi.org/10.1186/s13229-022-00502-9 |
| spellingShingle | Xiaoyun Sun Linxi Cheng Yuhua Sun Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF Molecular Autism |
| title | Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF |
| title_full | Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF |
| title_fullStr | Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF |
| title_full_unstemmed | Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF |
| title_short | Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF |
| title_sort | autism associated protein pogz controls escs and esc neural induction by association with esbaf |
| url | https://doi.org/10.1186/s13229-022-00502-9 |
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