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Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells

PAX6 is a highly conserved transcription factor and key regulator of several neurogenic processes, including the continuous generation of dopaminergic/GABAergic interneurons in the adult ventricular-subventricular (V-SVZ) neurogenic system in mice. Here we report that PAX6 cooperates with the TALE-h...

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Autores principales: Hau, Ann-Christin, Mommaerts, Elise, Laub, Vera, Müller, Tamara, Dittmar, Gunnar, Schulte, Dorothea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545929/
https://www.ncbi.nlm.nih.gov/pubmed/34697387
http://dx.doi.org/10.1038/s41598-021-99968-5
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author Hau, Ann-Christin
Mommaerts, Elise
Laub, Vera
Müller, Tamara
Dittmar, Gunnar
Schulte, Dorothea
author_facet Hau, Ann-Christin
Mommaerts, Elise
Laub, Vera
Müller, Tamara
Dittmar, Gunnar
Schulte, Dorothea
author_sort Hau, Ann-Christin
collection PubMed
description PAX6 is a highly conserved transcription factor and key regulator of several neurogenic processes, including the continuous generation of dopaminergic/GABAergic interneurons in the adult ventricular-subventricular (V-SVZ) neurogenic system in mice. Here we report that PAX6 cooperates with the TALE-homeodomain transcription factor PBX1 in this context. Chromatin-immunoprecipitation showed that PBX1 and PAX6 co-occupy shared genomic binding sites in adult V-SVZ stem- and progenitor cell cultures and mouse embryonic stem cells, while depletion of Pbx1 revealed that association of PAX6 with these sites requires the presence of PBX1. Expression profiling together with viral overexpression or knockdown of Pax6 or Pbx1 identified novel PBX1-PAX6 co-regulated genes, including several transcription factors. Computational modeling of genome wide expression identified novel cross-regulatory networks among these very transcription factors. Taken together, the results presented here highlight the intimate link that exists between PAX6 and TALE-HD family proteins and contribute novel insights into how the orchestrated activity of transcription factors shapes adult V-SVZ neurogenesis.
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spelling pubmed-85459292021-10-27 Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells Hau, Ann-Christin Mommaerts, Elise Laub, Vera Müller, Tamara Dittmar, Gunnar Schulte, Dorothea Sci Rep Article PAX6 is a highly conserved transcription factor and key regulator of several neurogenic processes, including the continuous generation of dopaminergic/GABAergic interneurons in the adult ventricular-subventricular (V-SVZ) neurogenic system in mice. Here we report that PAX6 cooperates with the TALE-homeodomain transcription factor PBX1 in this context. Chromatin-immunoprecipitation showed that PBX1 and PAX6 co-occupy shared genomic binding sites in adult V-SVZ stem- and progenitor cell cultures and mouse embryonic stem cells, while depletion of Pbx1 revealed that association of PAX6 with these sites requires the presence of PBX1. Expression profiling together with viral overexpression or knockdown of Pax6 or Pbx1 identified novel PBX1-PAX6 co-regulated genes, including several transcription factors. Computational modeling of genome wide expression identified novel cross-regulatory networks among these very transcription factors. Taken together, the results presented here highlight the intimate link that exists between PAX6 and TALE-HD family proteins and contribute novel insights into how the orchestrated activity of transcription factors shapes adult V-SVZ neurogenesis. Nature Publishing Group UK 2021-10-25 /pmc/articles/PMC8545929/ /pubmed/34697387 http://dx.doi.org/10.1038/s41598-021-99968-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hau, Ann-Christin
Mommaerts, Elise
Laub, Vera
Müller, Tamara
Dittmar, Gunnar
Schulte, Dorothea
Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells
title Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells
title_full Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells
title_fullStr Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells
title_full_unstemmed Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells
title_short Transcriptional cooperation of PBX1 and PAX6 in adult neural progenitor cells
title_sort transcriptional cooperation of pbx1 and pax6 in adult neural progenitor cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545929/
https://www.ncbi.nlm.nih.gov/pubmed/34697387
http://dx.doi.org/10.1038/s41598-021-99968-5
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