Balancing cohesin eviction and retention prevents aberrant chromosomal interactions, Polycomb-mediated repression, and X-inactivation
| Autor: | Jeannie T. Lee, Behnam Nabet, Andrea J. Kriz, David Colognori, Hongjae Sunwoo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
X Chromosome
Chromosomal Proteins Non-Histone Protein Conformation Polycomb-Group Proteins Cell Cycle Proteins Biology X-inactivation Article Cell Line 03 medical and health sciences Mice Structure-Activity Relationship 0302 clinical medicine X Chromosome Inactivation Gene silencing Animals Gene Silencing Molecular Biology Gene Psychological repression X chromosome Embryonic Stem Cells 030304 developmental biology 0303 health sciences Cohesin Proteins Cell Biology Cell biology Chromatin DNA-Binding Proteins Nucleic Acid Conformation XIST Female RNA Long Noncoding biological phenomena cell phenomena and immunity 030217 neurology & neurosurgery |
| Zdroj: | Mol Cell |
| Popis: | Depletion of architectural factors globally alters chromatin structure but only modestly affects gene expression. We revisit the structure-function relationship using the inactive X chromosome (Xi) as a model. We investigate cohesin imbalances by forcing its depletion or retention using degron-tagged RAD21 (cohesin subunit) or WAPL (cohesin release factor). Cohesin loss disrupts the Xi superstructure, unveiling superloops between escapee genes with minimal effect on gene repression. By contrast, forced cohesin retention markedly affects Xi superstructure, compromises spreading of Xist RNA-Polycomb complexes, and attenuates Xi silencing. Effects are greatest at distal chromosomal ends, where looping contacts with the Xist locus are weakened. Surprisingly, cohesin loss creates an Xi superloop, and cohesin retention creates Xi megadomains on the active X chromosome. Across the genome, a proper cohesin balance protects against aberrant inter-chromosomal interactions and tempers Polycomb-mediated repression. We conclude that a balance of cohesin eviction and retention regulates X inactivation and inter-chromosomal interactions across the genome. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|