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Transcription dynamically patterns the meiotic chromosome-axis interface.

Sun X, Huang L, Markowitz TE, Blitzblau HG, Chen D, Klein F, Hochwagen A - Elife (2015)

Bottom Line: We found that the axial element proteins of budding yeast are flexibly anchored to chromatin by the ring-like cohesin complex.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, New York University, New York, United States.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Ectopically expressed Scc1 localizes to the same sites as Rec8 in meiosis.Top panel: ChIP–chip analysis of Rec8-3HA in otherwise WT cells (green). Bottom panel: ChIP–chip analysis of 3HA-Scc1 in rec8Δ, pREC8-3HA-SCC1 mutant cells (purple). Signal along chromosome XII is depicted to allow comparison with the profiles shown in Figure 7C.DOI:http://dx.doi.org/10.7554/eLife.07424.014
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fig7s1: Ectopically expressed Scc1 localizes to the same sites as Rec8 in meiosis.Top panel: ChIP–chip analysis of Rec8-3HA in otherwise WT cells (green). Bottom panel: ChIP–chip analysis of 3HA-Scc1 in rec8Δ, pREC8-3HA-SCC1 mutant cells (purple). Signal along chromosome XII is depicted to allow comparison with the profiles shown in Figure 7C.DOI:http://dx.doi.org/10.7554/eLife.07424.014

Mentions: We asked whether the need for assembling a DSB-competent meiotic chromosome axis could be one reason why cells express a meiosis-specific form of cohesin. For this purpose, we replaced the only meiosis-specific subunit of cohesin, Rec8, with its mitotic counterpart Scc1/Mcd1 by deleting REC8 and expressing SCC1 from the REC8 promoter (pREC8-SCC1) (Toth et al., 2000). ChIP analysis revealed that Scc1-containing cohesin was targeted to the same chromosomal sites as Rec8-cohesin, indicating that Scc1 can fully substitute for Rec8 in recruiting cohesin to meiotic chromosomes (Pearson's r = 0.93, Figure 7—figure supplement 1). However, Scc1-cohesin did not efficiently recruit Red1 (Figure 7C). As a result, the DSB distribution of rec8Δ pREC8-SCC1 cells remained similar to rec8Δ mutants and unlike wild-type cells (Figure 7C). Consistent with this observation, Scc1 failed to detectably precipitate with V5-Red1 when expressed instead of Rec8 from the REC8-promoter (Figure 6F). We conclude that only meiotic cohesin can efficiently recruit meiotic axis proteins. Surprisingly, pREC8-SCC1 did restore transcriptional focusing to axis association sites (Figure 7D). These data indicate that focusing of axis proteins and axis protein recruitment are separable activities of meiotic cohesin and suggest that Rec8, but not Scc1, provides the necessary Red1 contacts for evenly distributing axis proteins, and thus recombination events, along meiotic chromosomes.


Transcription dynamically patterns the meiotic chromosome-axis interface.

Sun X, Huang L, Markowitz TE, Blitzblau HG, Chen D, Klein F, Hochwagen A - Elife (2015)

Ectopically expressed Scc1 localizes to the same sites as Rec8 in meiosis.Top panel: ChIP–chip analysis of Rec8-3HA in otherwise WT cells (green). Bottom panel: ChIP–chip analysis of 3HA-Scc1 in rec8Δ, pREC8-3HA-SCC1 mutant cells (purple). Signal along chromosome XII is depicted to allow comparison with the profiles shown in Figure 7C.DOI:http://dx.doi.org/10.7554/eLife.07424.014
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530585&req=5

fig7s1: Ectopically expressed Scc1 localizes to the same sites as Rec8 in meiosis.Top panel: ChIP–chip analysis of Rec8-3HA in otherwise WT cells (green). Bottom panel: ChIP–chip analysis of 3HA-Scc1 in rec8Δ, pREC8-3HA-SCC1 mutant cells (purple). Signal along chromosome XII is depicted to allow comparison with the profiles shown in Figure 7C.DOI:http://dx.doi.org/10.7554/eLife.07424.014
Mentions: We asked whether the need for assembling a DSB-competent meiotic chromosome axis could be one reason why cells express a meiosis-specific form of cohesin. For this purpose, we replaced the only meiosis-specific subunit of cohesin, Rec8, with its mitotic counterpart Scc1/Mcd1 by deleting REC8 and expressing SCC1 from the REC8 promoter (pREC8-SCC1) (Toth et al., 2000). ChIP analysis revealed that Scc1-containing cohesin was targeted to the same chromosomal sites as Rec8-cohesin, indicating that Scc1 can fully substitute for Rec8 in recruiting cohesin to meiotic chromosomes (Pearson's r = 0.93, Figure 7—figure supplement 1). However, Scc1-cohesin did not efficiently recruit Red1 (Figure 7C). As a result, the DSB distribution of rec8Δ pREC8-SCC1 cells remained similar to rec8Δ mutants and unlike wild-type cells (Figure 7C). Consistent with this observation, Scc1 failed to detectably precipitate with V5-Red1 when expressed instead of Rec8 from the REC8-promoter (Figure 6F). We conclude that only meiotic cohesin can efficiently recruit meiotic axis proteins. Surprisingly, pREC8-SCC1 did restore transcriptional focusing to axis association sites (Figure 7D). These data indicate that focusing of axis proteins and axis protein recruitment are separable activities of meiotic cohesin and suggest that Rec8, but not Scc1, provides the necessary Red1 contacts for evenly distributing axis proteins, and thus recombination events, along meiotic chromosomes.

Bottom Line: We found that the axial element proteins of budding yeast are flexibly anchored to chromatin by the ring-like cohesin complex.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, New York University, New York, United States.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus