A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming
PRDM14 is an important determinant of the human embryonic stem cell (ESC) identity and works in concert with the core ESC regulators to activate pluripotency-associated genes. PRDM14 has been previously reported to exhibit repressive activity in mouse ESCs and primordial germ cells; and while PRDM14...
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| Format: | Journal Article |
| Language: | English |
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2013
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| Online Access: | https://hdl.handle.net/10356/106858 http://hdl.handle.net/10220/17982 http://dx.doi.org/10.1002/stem.1307 |
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| author | Su, I-hsin Chan, Yun-Shen Göke, Jonathan Lu, Xinyi Venkatesan, Nandini Feng, Bo Ng, Huck-Hui |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Su, I-hsin Chan, Yun-Shen Göke, Jonathan Lu, Xinyi Venkatesan, Nandini Feng, Bo Ng, Huck-Hui |
| author_sort | Su, I-hsin |
| collection | NTU |
| description | PRDM14 is an important determinant of the human embryonic stem cell (ESC) identity and works in concert with the core ESC regulators to activate pluripotency-associated genes. PRDM14 has been previously reported to exhibit repressive activity in mouse ESCs and primordial germ cells; and while PRDM14 has been implicated to suppress differentiation genes in human ESCs, the exact mechanism of this repressive activity remains unknown. In this study, we provide evidence that PRDM14 is a direct repressor of developmental genes in human ESCs. PRDM14 binds to silenced genes in human ESCs and its global binding profile is enriched for the repressive trimethylation of histone H3 lysine 27 (H3K27me3) modification. Further investigation reveals that PRDM14 interacts directly with the chromatin regulator polycomb repressive complex 2 (PRC2) and PRC2 binding is detected at PRDM14-bound loci in human ESCs. Depletion of PRDM14 reduces PRC2 binding at these loci and the concomitant reduction of H3K27me3 modification. Using reporter assays, we demonstrate that gene loci bound by PRDM14 exhibit repressive activity that is dependent on both PRDM14 and PRC2. In reprogramming human fibroblasts into induced pluripotent stem cells (iPSCs), ectopically expressed PRDM14 can repress these developmental genes in fibroblasts. In addition, we show that PRDM14 recruits PRC2 to repress a key mesenchymal gene ZEB1, which enhances mesenchymal-to-epithelial transition in the initiation event of iPSC reprogramming. In summary, our study reveals a repressive role of PRDM14 in the maintenance and induction of pluripotency and identifies PRDM14 as a new regulator of PRC2. |
| first_indexed | 2024-10-01T04:16:50Z |
| format | Journal Article |
| id | ntu-10356/106858 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:16:50Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/1068582019-12-06T22:19:53Z A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming Su, I-hsin Chan, Yun-Shen Göke, Jonathan Lu, Xinyi Venkatesan, Nandini Feng, Bo Ng, Huck-Hui School of Biological Sciences DRNTU::Science::Biological sciences PRDM14 is an important determinant of the human embryonic stem cell (ESC) identity and works in concert with the core ESC regulators to activate pluripotency-associated genes. PRDM14 has been previously reported to exhibit repressive activity in mouse ESCs and primordial germ cells; and while PRDM14 has been implicated to suppress differentiation genes in human ESCs, the exact mechanism of this repressive activity remains unknown. In this study, we provide evidence that PRDM14 is a direct repressor of developmental genes in human ESCs. PRDM14 binds to silenced genes in human ESCs and its global binding profile is enriched for the repressive trimethylation of histone H3 lysine 27 (H3K27me3) modification. Further investigation reveals that PRDM14 interacts directly with the chromatin regulator polycomb repressive complex 2 (PRC2) and PRC2 binding is detected at PRDM14-bound loci in human ESCs. Depletion of PRDM14 reduces PRC2 binding at these loci and the concomitant reduction of H3K27me3 modification. Using reporter assays, we demonstrate that gene loci bound by PRDM14 exhibit repressive activity that is dependent on both PRDM14 and PRC2. In reprogramming human fibroblasts into induced pluripotent stem cells (iPSCs), ectopically expressed PRDM14 can repress these developmental genes in fibroblasts. In addition, we show that PRDM14 recruits PRC2 to repress a key mesenchymal gene ZEB1, which enhances mesenchymal-to-epithelial transition in the initiation event of iPSC reprogramming. In summary, our study reveals a repressive role of PRDM14 in the maintenance and induction of pluripotency and identifies PRDM14 as a new regulator of PRC2. 2013-12-02T08:17:34Z 2019-12-06T22:19:53Z 2013-12-02T08:17:34Z 2019-12-06T22:19:53Z 2013 2013 Journal Article Chan, Y.-S., Göke, J., Lu, X., Venkatesan, N., Feng, B., Su, I.-H., & Ng, H.-H. (2013). A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming. Stem cells, 31(4), 682-692. 1066-5099 https://hdl.handle.net/10356/106858 http://hdl.handle.net/10220/17982 http://dx.doi.org/10.1002/stem.1307 en Stem cells |
| spellingShingle | DRNTU::Science::Biological sciences Su, I-hsin Chan, Yun-Shen Göke, Jonathan Lu, Xinyi Venkatesan, Nandini Feng, Bo Ng, Huck-Hui A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming |
| title | A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming |
| title_full | A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming |
| title_fullStr | A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming |
| title_full_unstemmed | A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming |
| title_short | A PRC2-dependent repressive role of PRDM14 in human embryonic stem cells and induced pluripotent stem cell reprogramming |
| title_sort | prc2 dependent repressive role of prdm14 in human embryonic stem cells and induced pluripotent stem cell reprogramming |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/106858 http://hdl.handle.net/10220/17982 http://dx.doi.org/10.1002/stem.1307 |
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