Topological remodeling regulates X-chromosome gene expression

Sex chromosome type are different in male and female (XX, XY or ZW, ZZ) which results in somatic cells having different copies of X-link (or Z link) genes between different cell gender. To equalize the X-associate gene, C.elegan hermaphrodites (one sexual type of C elegan XX, the other is Male XO) down-regulate both X-chromosomes gene expressions to half fold, which is named dosage compensation. Previous studies majoring in this question were all at transcriptional and epigenetic level as a consequence of seeing DNA in linearity. However, Emily looked chromosome topologically. They for the first time acquire the 3D structure of both eu- and sex-chromosome and then addressed how to determine the high order chromosome structure to regulate gene expression.

In order to explore the X-chromosome topology, Emily and her colleagues used the Hi-C technology, which combines high throughput sequencing with a modified chromosome conformation capture protocol. To further test their Hi-C result, they used FISH (fluorescent in situ hybridization) to validate their conclusion.

Emily and her colleagues showed the X chromosomes were spatially organized during dosage compensation by forming more self-interact domain (also called topological associated domain, TAD in mammalian). In addition to this, they demonstrated the remodeling of X chromosome was achieved by the Dosage Compensation Complex (DCC) binding to the Rex DNA sequence. Finally, the author found the 3D chromosome remodeling during dosage compensation globally affected the X-line gene expression but not specifically affect the gene in or between the TAD boundaries.

Previous study with genetic tools has indicated both Dosage Compensation Complex and Rex site are required for the dosage compensation. In this paper Emily and her colleagues advanced this field and clarified this process was achieved by imposing a more organized 3D structure to the X chromosome. Moreover, the conclusion that dosage compensation dependent chromosome remodeling influences global but not local gene expression provides us new reason why one gene is able to affect multiple genes expression.


This work is published on Nature on July 9th 2015. To find more, please go to the web site

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