Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency
Abstract Nuclear architecture underlies the transcriptional programs within the cell to establish cell identity. As previously demonstrated, long-range chromatin interactions of the Oct4 distal enhancer (DE) are correlated with active transcription in naïve state embryonic stem cells. Here, we ident...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-02-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01363-8 |
| _version_ | 1797865573840846848 |
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| author | Byoung-San Moon David Huang Fan Gao Mingyang Cai Guochang Lyu Lei Zhang Jun Chen Wange Lu |
| author_facet | Byoung-San Moon David Huang Fan Gao Mingyang Cai Guochang Lyu Lei Zhang Jun Chen Wange Lu |
| author_sort | Byoung-San Moon |
| collection | DOAJ |
| description | Abstract Nuclear architecture underlies the transcriptional programs within the cell to establish cell identity. As previously demonstrated, long-range chromatin interactions of the Oct4 distal enhancer (DE) are correlated with active transcription in naïve state embryonic stem cells. Here, we identify and characterize extreme long-range interactions of the Oct4 DE through a novel CRISPR labeling technique we developed and chromosome conformation capture to identify lethal giant larvae 2 (Llgl2) and growth factor receptor-bound protein 7 (Grb7) as putative functional interacting target genes in different chromosomes. We show that the Oct4 DE directly regulates expression of Llgl2 and Grb7 in addition to Oct4. Expression of Llgl2 and Grb7 closely correlates with the pluripotent state, where knock down of either result in loss of pluripotency, and overexpression enhances somatic cell reprogramming. We demonstrated that biologically important interactions of the Oct4 DE can occur at extreme distances that are necessary for the maintenance of the pluripotent state. |
| first_indexed | 2024-04-09T23:11:23Z |
| format | Article |
| id | doaj.art-ee96c1692bd0487298c7416fff3bd225 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-09T23:11:23Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-ee96c1692bd0487298c7416fff3bd2252023-03-22T10:25:37ZengNature Publishing GroupCell Death Discovery2058-77162023-02-019111310.1038/s41420-023-01363-8Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotencyByoung-San Moon0David Huang1Fan Gao2Mingyang Cai3Guochang Lyu4Lei Zhang5Jun Chen6Wange Lu7Department of Biotechnology, Chonnam National UniversityDepartment of Stem Cell Biology and Regenerative Medicine, Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern CaliforniaDepartment of Stem Cell Biology and Regenerative Medicine, Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern CaliforniaDepartment of Stem Cell Biology and Regenerative Medicine, Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern CaliforniaDepartment of Stem Cell Biology and Regenerative Medicine, Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern CaliforniaState Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai UniversityDepartment of Stem Cell Biology and Regenerative Medicine, Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern CaliforniaAbstract Nuclear architecture underlies the transcriptional programs within the cell to establish cell identity. As previously demonstrated, long-range chromatin interactions of the Oct4 distal enhancer (DE) are correlated with active transcription in naïve state embryonic stem cells. Here, we identify and characterize extreme long-range interactions of the Oct4 DE through a novel CRISPR labeling technique we developed and chromosome conformation capture to identify lethal giant larvae 2 (Llgl2) and growth factor receptor-bound protein 7 (Grb7) as putative functional interacting target genes in different chromosomes. We show that the Oct4 DE directly regulates expression of Llgl2 and Grb7 in addition to Oct4. Expression of Llgl2 and Grb7 closely correlates with the pluripotent state, where knock down of either result in loss of pluripotency, and overexpression enhances somatic cell reprogramming. We demonstrated that biologically important interactions of the Oct4 DE can occur at extreme distances that are necessary for the maintenance of the pluripotent state.https://doi.org/10.1038/s41420-023-01363-8 |
| spellingShingle | Byoung-San Moon David Huang Fan Gao Mingyang Cai Guochang Lyu Lei Zhang Jun Chen Wange Lu Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency Cell Death Discovery |
| title | Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency |
| title_full | Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency |
| title_fullStr | Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency |
| title_full_unstemmed | Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency |
| title_short | Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency |
| title_sort | long range inter chromosomal interaction of oct4 distal enhancer loci regulates escs pluripotency |
| url | https://doi.org/10.1038/s41420-023-01363-8 |
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