SMCHD1 Merges Chromosome Compartments and Assists Formation of Super-Structures on the Inactive X
| Autor: | Teddy Jégu, Hyun Jung Oh, Chen-Yu Wang, Hsueh-Ping Chu, Jeannie T. Lee |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Chromosomal Proteins Non-Histone Mammalian Chromosomes Heterochromatic silencing Biology General Biochemistry Genetics and Molecular Biology X-inactivation Article Cell Line Histones 03 medical and health sciences Mice X Chromosome Inactivation Heterochromatin Animals Alleles Principal Component Analysis Nuclear organization Chromosome Mouse Embryonic Stem Cells DNA Methylation Chromosomes Mammalian Cell biology 030104 developmental biology XIST Female RNA Long Noncoding |
| Zdroj: | Cell. 174(2) |
| ISSN: | 1097-4172 |
| Popis: | Summary Mammalian chromosomes are partitioned into A/B compartments and topologically associated domains (TADs). The inactive X (Xi) chromosome, however, adopts a distinct conformation without evident compartments or TADs. Here, through exploration of an architectural protein, structural-maintenance-of-chromosomes hinge domain containing 1 (SMCHD1), we probe how the Xi is reconfigured during X chromosome inactivation. A/B compartments are first fused into "S1" and "S2" compartments, coinciding with Xist spreading into gene-rich domains. SMCHD1 then binds S1/S2 compartments and merges them to create a compartment-less architecture. Contrary to current views, TADs remain on the Xi but in an attenuated state. Ablating SMCHD1 results in a persistent S1/S2 organization and strengthening of TADs. Furthermore, loss of SMCHD1 causes regional defects in Xist spreading and erosion of heterochromatic silencing. We present a stepwise model for Xi folding, where SMCHD1 attenuates a hidden layer of Xi architecture to facilitate Xist spreading. |
| Databáze: | OpenAIRE |
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