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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

Genome-wide localization of meiotic axis proteins and cohesin.(A) Distribution of axis proteins and cohesins as determined by ChIP-seq. Chromosome XI is shown as an example to show co-enrichment with the exception of the centromere (indicated by black circle). Bottom panels are a zoom-in to show that axis proteins in general do not localize to DSB hotspots as measured by Thacker et al. (2014). (B) Pairwise correlation between Red1 ChIP and cohesin ChIP signals. (C) Red1 and Rec8 ChIP signal per bp as a function of chromosome length. 25 kb to either side of the centromeres were excluded from this analysis to avoid biases caused by the strong centromere-proximal enrichment of Rec8 (see A). The three shortest chromosomes are displayed as solid dots. (D) Numbers of Red1 peaks (see ‘Materials and methods’ for peak calling) were correlated (Pearson's r) with the numbers of DSB hotspots on each chromosome. (E) Distribution of widths for 774 Red1 peaks. (F) Spo11 oligos (green) were strongly depleted at the axis protein associated regions (red). Average Spo11 oligo density is plotted as a function of distance from Red1 peak summits. Red1 signals were averaged among all the peaks. (G) Percentage of Red1 peaks (top) and DSB hotspots (bottom) in different positions relative to genes. Peaks were defined as a 500 bp-surrounding region of summits. 5′ regions of genes were defined as 500 bp upstream of the start codons, and 3′ regions of genes were defined as 250 bp on either side of the stop codons. Divergent (Div.) or convergent (Conv.) regions refer to the intergenic areas between two adjacent start or stop codons, respectively. (H) Putative motif at axis sites. Top: motif derived from Red1 ChIP-seq using MEME-ChIP (Machanick and Bailey, 2011). Bottom: probability of motif occurrence around Red1 peak summits.DOI:http://dx.doi.org/10.7554/eLife.07424.004
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fig1s1: Genome-wide localization of meiotic axis proteins and cohesin.(A) Distribution of axis proteins and cohesins as determined by ChIP-seq. Chromosome XI is shown as an example to show co-enrichment with the exception of the centromere (indicated by black circle). Bottom panels are a zoom-in to show that axis proteins in general do not localize to DSB hotspots as measured by Thacker et al. (2014). (B) Pairwise correlation between Red1 ChIP and cohesin ChIP signals. (C) Red1 and Rec8 ChIP signal per bp as a function of chromosome length. 25 kb to either side of the centromeres were excluded from this analysis to avoid biases caused by the strong centromere-proximal enrichment of Rec8 (see A). The three shortest chromosomes are displayed as solid dots. (D) Numbers of Red1 peaks (see ‘Materials and methods’ for peak calling) were correlated (Pearson's r) with the numbers of DSB hotspots on each chromosome. (E) Distribution of widths for 774 Red1 peaks. (F) Spo11 oligos (green) were strongly depleted at the axis protein associated regions (red). Average Spo11 oligo density is plotted as a function of distance from Red1 peak summits. Red1 signals were averaged among all the peaks. (G) Percentage of Red1 peaks (top) and DSB hotspots (bottom) in different positions relative to genes. Peaks were defined as a 500 bp-surrounding region of summits. 5′ regions of genes were defined as 500 bp upstream of the start codons, and 3′ regions of genes were defined as 250 bp on either side of the stop codons. Divergent (Div.) or convergent (Conv.) regions refer to the intergenic areas between two adjacent start or stop codons, respectively. (H) Putative motif at axis sites. Top: motif derived from Red1 ChIP-seq using MEME-ChIP (Machanick and Bailey, 2011). Bottom: probability of motif occurrence around Red1 peak summits.DOI:http://dx.doi.org/10.7554/eLife.07424.004

Mentions: We used chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to determine the chromosomal distribution of two axis proteins, Red1 and Hop1, as well as two cohesin subunits, Rec8 and Smc3. To validate our data, we compared the resulting profiles with previous lower-resolution ChIP–chip data of Hop1, Red1, and Rec8 (Blitzblau et al., 2012). A high correlation indicated that the identification of axis association sites was consistent between the two approaches (Pearson's r = 0.80). As observed previously, the genome-wide distribution of axis proteins and cohesin was highly correlated (Figure 1—figure supplement 1A,B), with the exception of centromeric regions where cohesin was more highly enriched than axis proteins. Because of the high correspondence in localization, we chose the Red1 data set as the representative axis protein data set for subsequent analyses.


Transcription dynamically patterns the meiotic chromosome-axis interface.

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

Genome-wide localization of meiotic axis proteins and cohesin.(A) Distribution of axis proteins and cohesins as determined by ChIP-seq. Chromosome XI is shown as an example to show co-enrichment with the exception of the centromere (indicated by black circle). Bottom panels are a zoom-in to show that axis proteins in general do not localize to DSB hotspots as measured by Thacker et al. (2014). (B) Pairwise correlation between Red1 ChIP and cohesin ChIP signals. (C) Red1 and Rec8 ChIP signal per bp as a function of chromosome length. 25 kb to either side of the centromeres were excluded from this analysis to avoid biases caused by the strong centromere-proximal enrichment of Rec8 (see A). The three shortest chromosomes are displayed as solid dots. (D) Numbers of Red1 peaks (see ‘Materials and methods’ for peak calling) were correlated (Pearson's r) with the numbers of DSB hotspots on each chromosome. (E) Distribution of widths for 774 Red1 peaks. (F) Spo11 oligos (green) were strongly depleted at the axis protein associated regions (red). Average Spo11 oligo density is plotted as a function of distance from Red1 peak summits. Red1 signals were averaged among all the peaks. (G) Percentage of Red1 peaks (top) and DSB hotspots (bottom) in different positions relative to genes. Peaks were defined as a 500 bp-surrounding region of summits. 5′ regions of genes were defined as 500 bp upstream of the start codons, and 3′ regions of genes were defined as 250 bp on either side of the stop codons. Divergent (Div.) or convergent (Conv.) regions refer to the intergenic areas between two adjacent start or stop codons, respectively. (H) Putative motif at axis sites. Top: motif derived from Red1 ChIP-seq using MEME-ChIP (Machanick and Bailey, 2011). Bottom: probability of motif occurrence around Red1 peak summits.DOI:http://dx.doi.org/10.7554/eLife.07424.004
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Related In: Results  -  Collection

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fig1s1: Genome-wide localization of meiotic axis proteins and cohesin.(A) Distribution of axis proteins and cohesins as determined by ChIP-seq. Chromosome XI is shown as an example to show co-enrichment with the exception of the centromere (indicated by black circle). Bottom panels are a zoom-in to show that axis proteins in general do not localize to DSB hotspots as measured by Thacker et al. (2014). (B) Pairwise correlation between Red1 ChIP and cohesin ChIP signals. (C) Red1 and Rec8 ChIP signal per bp as a function of chromosome length. 25 kb to either side of the centromeres were excluded from this analysis to avoid biases caused by the strong centromere-proximal enrichment of Rec8 (see A). The three shortest chromosomes are displayed as solid dots. (D) Numbers of Red1 peaks (see ‘Materials and methods’ for peak calling) were correlated (Pearson's r) with the numbers of DSB hotspots on each chromosome. (E) Distribution of widths for 774 Red1 peaks. (F) Spo11 oligos (green) were strongly depleted at the axis protein associated regions (red). Average Spo11 oligo density is plotted as a function of distance from Red1 peak summits. Red1 signals were averaged among all the peaks. (G) Percentage of Red1 peaks (top) and DSB hotspots (bottom) in different positions relative to genes. Peaks were defined as a 500 bp-surrounding region of summits. 5′ regions of genes were defined as 500 bp upstream of the start codons, and 3′ regions of genes were defined as 250 bp on either side of the stop codons. Divergent (Div.) or convergent (Conv.) regions refer to the intergenic areas between two adjacent start or stop codons, respectively. (H) Putative motif at axis sites. Top: motif derived from Red1 ChIP-seq using MEME-ChIP (Machanick and Bailey, 2011). Bottom: probability of motif occurrence around Red1 peak summits.DOI:http://dx.doi.org/10.7554/eLife.07424.004
Mentions: We used chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to determine the chromosomal distribution of two axis proteins, Red1 and Hop1, as well as two cohesin subunits, Rec8 and Smc3. To validate our data, we compared the resulting profiles with previous lower-resolution ChIP–chip data of Hop1, Red1, and Rec8 (Blitzblau et al., 2012). A high correlation indicated that the identification of axis association sites was consistent between the two approaches (Pearson's r = 0.80). As observed previously, the genome-wide distribution of axis proteins and cohesin was highly correlated (Figure 1—figure supplement 1A,B), with the exception of centromeric regions where cohesin was more highly enriched than axis proteins. Because of the high correspondence in localization, we chose the Red1 data set as the representative axis protein data set for subsequent analyses.

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