KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation
Trophoblast stem (TS) cells derived from the trophectoderm (TE) of mammalian embryos have the ability to self-renew indefinitely or differentiate into fetal lineages of the placenta. Epigenetic control of gene expression plays an instrumental role in dictating the fate of TS cell self-renewal and di...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2018-05-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/7/5/bio031245 |
| _version_ | 1818672670083907584 |
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| author | Jian Xu Benjamin L. Kidder |
| author_facet | Jian Xu Benjamin L. Kidder |
| author_sort | Jian Xu |
| collection | DOAJ |
| description | Trophoblast stem (TS) cells derived from the trophectoderm (TE) of mammalian embryos have the ability to self-renew indefinitely or differentiate into fetal lineages of the placenta. Epigenetic control of gene expression plays an instrumental role in dictating the fate of TS cell self-renewal and differentiation. However, the roles of histone demethylases and activating histone modifications such as methylation of histone 3 lysine 4 (H3K4me3/me2) in regulating TS cell expression programs, and in priming the epigenetic landscape for trophoblast differentiation, are largely unknown. Here, we demonstrate that the H3K4 demethylase, KDM5B, regulates the H3K4 methylome and expression landscapes of TS cells. Depletion of KDM5B resulted in downregulation of TS cell self-renewal genes and upregulation of trophoblast-lineage genes, which was accompanied by altered H3K4 methylation. Moreover, we found that KDM5B resets the H3K4 methylation landscape during differentiation in the absence of the external self-renewal signal, FGF4, by removing H3K4 methylation from promoters of self-renewal genes, and of genes whose expression is enriched in TS cells. Altogether, our data indicate an epigenetic role for KDM5B in regulating H3K4 methylation in TS cells and during trophoblast differentiation. |
| first_indexed | 2024-12-17T07:43:35Z |
| format | Article |
| id | doaj.art-d9790db94ef4432b9ae7da02aeab3866 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T07:43:35Z |
| publishDate | 2018-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-d9790db94ef4432b9ae7da02aeab38662022-12-21T21:58:04ZengThe Company of BiologistsBiology Open2046-63902018-05-017510.1242/bio.031245031245KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiationJian Xu0Benjamin L. Kidder1 Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA Trophoblast stem (TS) cells derived from the trophectoderm (TE) of mammalian embryos have the ability to self-renew indefinitely or differentiate into fetal lineages of the placenta. Epigenetic control of gene expression plays an instrumental role in dictating the fate of TS cell self-renewal and differentiation. However, the roles of histone demethylases and activating histone modifications such as methylation of histone 3 lysine 4 (H3K4me3/me2) in regulating TS cell expression programs, and in priming the epigenetic landscape for trophoblast differentiation, are largely unknown. Here, we demonstrate that the H3K4 demethylase, KDM5B, regulates the H3K4 methylome and expression landscapes of TS cells. Depletion of KDM5B resulted in downregulation of TS cell self-renewal genes and upregulation of trophoblast-lineage genes, which was accompanied by altered H3K4 methylation. Moreover, we found that KDM5B resets the H3K4 methylation landscape during differentiation in the absence of the external self-renewal signal, FGF4, by removing H3K4 methylation from promoters of self-renewal genes, and of genes whose expression is enriched in TS cells. Altogether, our data indicate an epigenetic role for KDM5B in regulating H3K4 methylation in TS cells and during trophoblast differentiation.http://bio.biologists.org/content/7/5/bio031245Trophoblast stem cellsMultipotentEpigeneticsChromatinChIP-SeqKDM5BH3K4me3DifferentiationHistone demethylase |
| spellingShingle | Jian Xu Benjamin L. Kidder KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation Biology Open Trophoblast stem cells Multipotent Epigenetics Chromatin ChIP-Seq KDM5B H3K4me3 Differentiation Histone demethylase |
| title | KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation |
| title_full | KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation |
| title_fullStr | KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation |
| title_full_unstemmed | KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation |
| title_short | KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation |
| title_sort | kdm5b decommissions the h3k4 methylation landscape of self renewal genes during trophoblast stem cell differentiation |
| topic | Trophoblast stem cells Multipotent Epigenetics Chromatin ChIP-Seq KDM5B H3K4me3 Differentiation Histone demethylase |
| url | http://bio.biologists.org/content/7/5/bio031245 |
| work_keys_str_mv | AT jianxu kdm5bdecommissionstheh3k4methylationlandscapeofselfrenewalgenesduringtrophoblaststemcelldifferentiation AT benjaminlkidder kdm5bdecommissionstheh3k4methylationlandscapeofselfrenewalgenesduringtrophoblaststemcelldifferentiation |