Transcription dynamically patterns the meiotic chromosome-axis interface.
Transcription dynamically patterns the meiotic chromosome-axis interface.
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DOI：
10.7554/elife.07424
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发表时间：
2015-08-10
期刊：
影响因子：
7.7
通讯作者：
Hochwagen A
中科院分区：
文献类型：
--
作者：
Sun X;Huang L;Markowitz TE;Blitzblau HG;Chen D;Klein F;Hochwagen A
Meiotic chromosomes are highly compacted yet remain transcriptionally active. To understand how chromosome folding accommodates transcription, we investigated the assembly of the axial element, the proteinaceous structure that compacts meiotic chromosomes and promotes recombination and fertility. We found that the axial element proteins of budding yeast are flexibly anchored to chromatin by the ring-like cohesin complex. The ubiquitous presence of cohesin at sites of convergent transcription provides well-dispersed points for axis attachment and thus chromosome compaction. Axis protein enrichment at these sites directly correlates with the propensity for recombination initiation nearby. A separate modulating mechanism that requires the conserved axial-element component Hop1 biases axis protein binding towards small chromosomes. Importantly, axis anchoring by cohesin is adjustable and readily displaced in the direction of transcription by the transcriptional machinery. We propose that such robust but flexible tethering allows the axial element to promote recombination while easily adapting to changes in chromosome activity. DOI: http://dx.doi.org/10.7554/eLife.07424.001 Chromosomes are long molecules of DNA that represent the genetic material of an organism. In most animal cells, chromosomes are found in pairs; with one inherited from the mother and the other from the father. Sex cells—egg cells and sperm—contain half the normal number of chromosomes, so that when they fuse, the resulting single-celled embryo inherits the full set. When sex cells are being produced, a ring made from a protein called cohesin encircles each pair of chromosomes and holds them together until they are ready to be separated. The paired chromosomes also swap sections of DNA via a process called recombination. Structures, referred to as axial elements, compact the chromosomes in each pair and bring them in close contact so that recombination can take place. In the sexually reproducing baker's yeast, axial elements contain three main proteins: cohesin, Hop1, and Red1, but it remains unclear how the entire structure is anchored to the underlying chromosomes. Furthermore, the genes encoded within the DNA of the compacted chromosomes remain active, but it is also not clear how this is possible. This is because the compacted structure would be expected to prevent the molecular machinery that expresses genes from accessing the DNA. Sun, Huang et al. have now studied this process in budding yeast cells by using a method called ChIP-seq to determine where cohesin and the Hop1 and Red1 proteins are found along the chromosomes. The experiments showed that cohesin, Hop1, and Red1 are enriched in regions between two genes that run in the opposite directions to each other. Sun, Huang et al. also observed that cohesin recruits Red1, which in turn, recruits Hop1, and that all three proteins physically interact with one another. These findings imply that it is cohesin that anchors the axial elements to the underlying chromosomes. Further experiments showed that cohesin slides along chromosomes towards areas where genes are active. This suggests that cohesin provides a robust, but flexible, link between the axial elements and the chromosomes. This flexibility would enable recombination and gene expression to continue in compacted chromosomes. A loss of flexibility may be one of the reasons why mutations in cohesin components of the axial element cause infertility in men and condition called premature ovarian failure in women. DOI: http://dx.doi.org/10.7554/eLife.07424.002
