Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development
Summary: The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by env...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-11-01
|
| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117304320 |
| _version_ | 1819040345513525248 |
|---|---|
| author | Manolis Gialitakis Mauro Tolaini Ying Li Mercedes Pardo Lu Yu Ana Toribio Jyoti S. Choudhary Kathy Niakan Venizelos Papayannopoulos Brigitta Stockinger |
| author_facet | Manolis Gialitakis Mauro Tolaini Ying Li Mercedes Pardo Lu Yu Ana Toribio Jyoti S. Choudhary Kathy Niakan Venizelos Papayannopoulos Brigitta Stockinger |
| author_sort | Manolis Gialitakis |
| collection | DOAJ |
| description | Summary: The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants; however, the precise molecular mechanisms remain unknown. The aryl hydrocarbon receptor (AHR) is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression. Here, we have investigated the AHR interactome in embryonic stem cells by mass spectrometry and show that ectopic activation of AHR during early differentiation disrupts the differentiation program via the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylation). The activated AHR/NuRD complex altered the expression of differentiation-specific genes that control the first two developmental decisions without affecting the pluripotency program. These findings identify a mechanism that allows environmental stimuli to disrupt embryonic development through AHR signaling. : In this article, Gialitakis and colleagues show that activation of the transcription factor AHR affects lineage decisions in embryonic stem cells. Activated AHR interacts with the NuRD complex and thereby transiently disrupts early stages of differentiation. Environmental pollutants that are poorly metabolized prolong the normally tightly controlled AHR activity and could therefore have adverse effects on mammalian development. Keywords: AHR, interactome, NuRD, embryonic development, environmental pollutants |
| first_indexed | 2024-12-21T09:07:38Z |
| format | Article |
| id | doaj.art-c1f5e94d893f497a94eab71322cbbe71 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-21T09:07:38Z |
| publishDate | 2017-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-c1f5e94d893f497a94eab71322cbbe712022-12-21T19:09:19ZengElsevierStem Cell Reports2213-67112017-11-019513771386Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic DevelopmentManolis Gialitakis0Mauro Tolaini1Ying Li2Mercedes Pardo3Lu Yu4Ana Toribio5Jyoti S. Choudhary6Kathy Niakan7Venizelos Papayannopoulos8Brigitta Stockinger9The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK; Corresponding authorThe Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UKThe Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UKProteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA Cambridgeshire, UKProteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA Cambridgeshire, UKProteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA Cambridgeshire, UKProteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA Cambridgeshire, UKThe Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UKThe Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UKThe Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK; Corresponding authorSummary: The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants; however, the precise molecular mechanisms remain unknown. The aryl hydrocarbon receptor (AHR) is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression. Here, we have investigated the AHR interactome in embryonic stem cells by mass spectrometry and show that ectopic activation of AHR during early differentiation disrupts the differentiation program via the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylation). The activated AHR/NuRD complex altered the expression of differentiation-specific genes that control the first two developmental decisions without affecting the pluripotency program. These findings identify a mechanism that allows environmental stimuli to disrupt embryonic development through AHR signaling. : In this article, Gialitakis and colleagues show that activation of the transcription factor AHR affects lineage decisions in embryonic stem cells. Activated AHR interacts with the NuRD complex and thereby transiently disrupts early stages of differentiation. Environmental pollutants that are poorly metabolized prolong the normally tightly controlled AHR activity and could therefore have adverse effects on mammalian development. Keywords: AHR, interactome, NuRD, embryonic development, environmental pollutantshttp://www.sciencedirect.com/science/article/pii/S2213671117304320 |
| spellingShingle | Manolis Gialitakis Mauro Tolaini Ying Li Mercedes Pardo Lu Yu Ana Toribio Jyoti S. Choudhary Kathy Niakan Venizelos Papayannopoulos Brigitta Stockinger Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development Stem Cell Reports |
| title | Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development |
| title_full | Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development |
| title_fullStr | Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development |
| title_full_unstemmed | Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development |
| title_short | Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development |
| title_sort | activation of the aryl hydrocarbon receptor interferes with early embryonic development |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117304320 |
| work_keys_str_mv | AT manolisgialitakis activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT maurotolaini activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT yingli activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT mercedespardo activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT luyu activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT anatoribio activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT jyotischoudhary activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT kathyniakan activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT venizelospapayannopoulos activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment AT brigittastockinger activationofthearylhydrocarbonreceptorinterfereswithearlyembryonicdevelopment |