Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression.
The relationship between cohesin-mediated chromatin looping and gene expression remains unclear. NIPBL and WAPL are two opposing regulators of cohesin activity; depletion of either is associated with changes in both chromatin folding and transcription across a wide range of cell types. However, a di...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-11-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010528 |
| _version_ | 1828083693014482944 |
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| author | Jennifer M Luppino Andrew Field Son C Nguyen Daniel S Park Parisha P Shah Richard J Abdill Yemin Lan Rebecca Yunker Rajan Jain Karen Adelman Eric F Joyce |
| author_facet | Jennifer M Luppino Andrew Field Son C Nguyen Daniel S Park Parisha P Shah Richard J Abdill Yemin Lan Rebecca Yunker Rajan Jain Karen Adelman Eric F Joyce |
| author_sort | Jennifer M Luppino |
| collection | DOAJ |
| description | The relationship between cohesin-mediated chromatin looping and gene expression remains unclear. NIPBL and WAPL are two opposing regulators of cohesin activity; depletion of either is associated with changes in both chromatin folding and transcription across a wide range of cell types. However, a direct comparison of their individual and combined effects on gene expression in the same cell type is lacking. We find that NIPBL or WAPL depletion in human HCT116 cells each alter the expression of ~2,000 genes, with only ~30% of the genes shared between the conditions. We find that clusters of differentially expressed genes within the same topologically associated domain (TAD) show coordinated misexpression, suggesting some genomic domains are especially sensitive to both more or less cohesin. Finally, co-depletion of NIPBL and WAPL restores the majority of gene misexpression as compared to either knockdown alone. A similar set of NIPBL-sensitive genes are rescued following CTCF co-depletion. Together, this indicates that altered transcription due to reduced cohesin activity can be functionally offset by removal of either its negative regulator (WAPL) or the physical barriers (CTCF) that restrict loop-extrusion events. |
| first_indexed | 2024-04-11T04:11:52Z |
| format | Article |
| id | doaj.art-6f10829c89194c2f98ca805aea9865a4 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-11T04:11:52Z |
| publishDate | 2022-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-6f10829c89194c2f98ca805aea9865a42023-01-01T05:32:03ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-11-011811e101052810.1371/journal.pgen.1010528Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression.Jennifer M LuppinoAndrew FieldSon C NguyenDaniel S ParkParisha P ShahRichard J AbdillYemin LanRebecca YunkerRajan JainKaren AdelmanEric F JoyceThe relationship between cohesin-mediated chromatin looping and gene expression remains unclear. NIPBL and WAPL are two opposing regulators of cohesin activity; depletion of either is associated with changes in both chromatin folding and transcription across a wide range of cell types. However, a direct comparison of their individual and combined effects on gene expression in the same cell type is lacking. We find that NIPBL or WAPL depletion in human HCT116 cells each alter the expression of ~2,000 genes, with only ~30% of the genes shared between the conditions. We find that clusters of differentially expressed genes within the same topologically associated domain (TAD) show coordinated misexpression, suggesting some genomic domains are especially sensitive to both more or less cohesin. Finally, co-depletion of NIPBL and WAPL restores the majority of gene misexpression as compared to either knockdown alone. A similar set of NIPBL-sensitive genes are rescued following CTCF co-depletion. Together, this indicates that altered transcription due to reduced cohesin activity can be functionally offset by removal of either its negative regulator (WAPL) or the physical barriers (CTCF) that restrict loop-extrusion events.https://doi.org/10.1371/journal.pgen.1010528 |
| spellingShingle | Jennifer M Luppino Andrew Field Son C Nguyen Daniel S Park Parisha P Shah Richard J Abdill Yemin Lan Rebecca Yunker Rajan Jain Karen Adelman Eric F Joyce Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression. PLoS Genetics |
| title | Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression. |
| title_full | Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression. |
| title_fullStr | Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression. |
| title_full_unstemmed | Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression. |
| title_short | Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression. |
| title_sort | co depletion of nipbl and wapl balance cohesin activity to correct gene misexpression |
| url | https://doi.org/10.1371/journal.pgen.1010528 |
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