Projects per year
Abstract / Description of output
Higher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures are unknown. A stable matrix underpinning nuclear organization was hypothesized, but the idea was abandoned as more dynamic models of chromatin behavior became prevalent. Here, we report that scaffold attachment factor A (SAF-A), originally identified as a structural nuclear protein, interacts with chromatin-associated RNAs (caRNAs) via its RGG domain to regulate human interphase chromatin structures in a transcription-dependent manner. Mechanistically, this is dependent on SAF-A’s AAA+ ATPase domain, which mediates cycles of protein oligomerization with caRNAs, in response to ATP binding and hydrolysis. SAF-A oligomerization decompacts large-scale chromatin structure while SAF-A loss or monomerization promotes aberrant chromosome folding and accumulation of genome damage. Our results show that SAF-A and caRNAs form a dynamic, transcriptionally responsive chromatin mesh that organizes large-scale chromosome structures and protects the genome from instability.
Original language | English |
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Pages (from-to) | 1214-1227.e18 |
Number of pages | 22 |
Journal | Cell |
Volume | 169 |
Issue number | 7 |
Early online date | 15 Jun 2017 |
DOIs | |
Publication status | Published - 15 Jun 2017 |
Keywords / Materials (for Non-textual outputs)
- Journal Article
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Dive into the research topics of 'SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs'. Together they form a unique fingerprint.Projects
- 1 Finished
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Understanding the regulation and topological organisation of DNA in the human genome
1/08/12 → 31/07/19
Project: Research