Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons

Abstract Chromatin architecture influences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic differentiation have identified coding genes, but the relationship with non-coding genes or chromatin accessibi...

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Autores principales:	César Meléndez-Ramírez, Raquel Cuevas-Diaz Duran, Tonatiuh Barrios-García, Mayela Giacoman-Lozano, Adolfo López-Ornelas, Jessica Herrera-Gamboa, Enrique Estudillo, Ernesto Soto-Reyes, Iván Velasco, Víctor Treviño
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8034529d3b8742349d5a37f35ded150d
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spelling	oai:doaj.org-article:8034529d3b8742349d5a37f35ded150d2021-12-02T17:08:44ZDynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons10.1038/s41598-021-96263-12045-2322https://doaj.org/article/8034529d3b8742349d5a37f35ded150d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96263-1https://doaj.org/toc/2045-2322Abstract Chromatin architecture influences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic differentiation have identified coding genes, but the relationship with non-coding genes or chromatin accessibility remains elusive. Using RNA-Seq and ATAC-Seq we profiled differentially expressed transcripts and open chromatin regions during early dopaminergic neuron differentiation. Hierarchical clustering of differentially expressed genes, resulted in 6 groups with unique characteristics. Surprisingly, the abundance of long non-coding RNAs (lncRNAs) was high in the most downregulated transcripts, and depicted positive correlations with target mRNAs. We observed that open chromatin regions decrease upon differentiation. Enrichment analyses of accessibility depict an association between open chromatin regions and specific functional pathways and gene-sets. A bioinformatic search for motifs allowed us to identify transcription factors and structural nuclear proteins that potentially regulate dopaminergic differentiation. Interestingly, we also found changes in protein and mRNA abundance of the CCCTC-binding factor, CTCF, which participates in genome organization and gene expression. Furthermore, assays demonstrated co-localization of CTCF with Polycomb-repressed chromatin marked by H3K27me3 in pluripotent cells, progressively decreasing in neural precursor cells and differentiated neurons. Our work provides a unique resource of transcription factors and regulatory elements, potentially involved in the acquisition of human dopaminergic neuron cell identity.César Meléndez-RamírezRaquel Cuevas-Diaz DuranTonatiuh Barrios-GarcíaMayela Giacoman-LozanoAdolfo López-OrnelasJessica Herrera-GamboaEnrique EstudilloErnesto Soto-ReyesIván VelascoVíctor TreviñoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q César Meléndez-Ramírez Raquel Cuevas-Diaz Duran Tonatiuh Barrios-García Mayela Giacoman-Lozano Adolfo López-Ornelas Jessica Herrera-Gamboa Enrique Estudillo Ernesto Soto-Reyes Iván Velasco Víctor Treviño Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons
description	Abstract Chromatin architecture influences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic differentiation have identified coding genes, but the relationship with non-coding genes or chromatin accessibility remains elusive. Using RNA-Seq and ATAC-Seq we profiled differentially expressed transcripts and open chromatin regions during early dopaminergic neuron differentiation. Hierarchical clustering of differentially expressed genes, resulted in 6 groups with unique characteristics. Surprisingly, the abundance of long non-coding RNAs (lncRNAs) was high in the most downregulated transcripts, and depicted positive correlations with target mRNAs. We observed that open chromatin regions decrease upon differentiation. Enrichment analyses of accessibility depict an association between open chromatin regions and specific functional pathways and gene-sets. A bioinformatic search for motifs allowed us to identify transcription factors and structural nuclear proteins that potentially regulate dopaminergic differentiation. Interestingly, we also found changes in protein and mRNA abundance of the CCCTC-binding factor, CTCF, which participates in genome organization and gene expression. Furthermore, assays demonstrated co-localization of CTCF with Polycomb-repressed chromatin marked by H3K27me3 in pluripotent cells, progressively decreasing in neural precursor cells and differentiated neurons. Our work provides a unique resource of transcription factors and regulatory elements, potentially involved in the acquisition of human dopaminergic neuron cell identity.
format	article
author	César Meléndez-Ramírez Raquel Cuevas-Diaz Duran Tonatiuh Barrios-García Mayela Giacoman-Lozano Adolfo López-Ornelas Jessica Herrera-Gamboa Enrique Estudillo Ernesto Soto-Reyes Iván Velasco Víctor Treviño
author_facet	César Meléndez-Ramírez Raquel Cuevas-Diaz Duran Tonatiuh Barrios-García Mayela Giacoman-Lozano Adolfo López-Ornelas Jessica Herrera-Gamboa Enrique Estudillo Ernesto Soto-Reyes Iván Velasco Víctor Treviño
author_sort	César Meléndez-Ramírez
title	Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons
title_short	Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons
title_full	Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons
title_fullStr	Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons
title_full_unstemmed	Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons
title_sort	dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8034529d3b8742349d5a37f35ded150d
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Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons

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