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Global chromatin domain organization of the Drosophila genome.

de Wit E, Braunschweig U, Greil F, Bussemaker HJ, van Steensel B - PLoS Genet. (2008)

Bottom Line: Furthermore, during evolution fewer chromosomal rearrangements occur inside chromatin domains than outside domains.Our results indicate that a substantial portion of the Drosophila genome is packaged into functionally coherent, multi-gene chromatin domains.This has broad mechanistic implications for gene regulation and genome evolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

ABSTRACT
In eukaryotes, neighboring genes can be packaged together in specific chromatin structures that ensure their coordinated expression. Examples of such multi-gene chromatin domains are well-documented, but a global view of the chromatin organization of eukaryotic genomes is lacking. To systematically identify multi-gene chromatin domains, we constructed a compendium of genome-scale binding maps for a broad panel of chromatin-associated proteins in Drosophila melanogaster. Next, we computationally analyzed this compendium for evidence of multi-gene chromatin domains using a novel statistical segmentation algorithm. We find that at least 50% of all fly genes are organized into chromatin domains, which often consist of dozens of genes. The domains are characterized by various known and novel combinations of chromatin proteins. The genes in many of the domains are coregulated during development and tend to have similar biological functions. Furthermore, during evolution fewer chromosomal rearrangements occur inside chromatin domains than outside domains. Our results indicate that a substantial portion of the Drosophila genome is packaged into functionally coherent, multi-gene chromatin domains. This has broad mechanistic implications for gene regulation and genome evolution.

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BRICK locations for all tested proteins.A) BRICKs on chromosome arm 2L. BRICKs smaller than 100 probed genes are shown for all analyzed proteins. The proteins are ordered by hierarchical clustering, with proteins that have the strongest overlapping domains closest together in the figure. B) Combined overview of the BRICKs for all proteins on all chromosome arms. BRICKs of different proteins are color-coded as indicated. Vertical position corresponds to the number of genes contained in the BRICK. Note that a substantial part of the Drosophila genome (∼50%) is covered by at least one BRICK.
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pgen-1000045-g004: BRICK locations for all tested proteins.A) BRICKs on chromosome arm 2L. BRICKs smaller than 100 probed genes are shown for all analyzed proteins. The proteins are ordered by hierarchical clustering, with proteins that have the strongest overlapping domains closest together in the figure. B) Combined overview of the BRICKs for all proteins on all chromosome arms. BRICKs of different proteins are color-coded as indicated. Vertical position corresponds to the number of genes contained in the BRICK. Note that a substantial part of the Drosophila genome (∼50%) is covered by at least one BRICK.

Mentions: To compare the spatial binding patterns of the 29 tested proteins and histone marks, we used a visual representation in which their respective BRICKs are stacked, providing a compact simultaneous view of their chromosomal domain structure (Fig. 4A and Supplementary Fig. S4). This revealed that several proteins have strongly overlapping BRICKs, suggesting that these proteins may act together to form a distinct chromatin domain. As expected, heterochromatin components HP1, Su(var)3-9, HP3/Lhr, HP4, HP5 and HP6 colocalize in BRICKS in pericentric regions (Supplementary Fig. S4) and can also be seen to form a small consistent domain at position ∼8 Mb on chromosome 2L (Fig. 4A). Likewise, the BRICK structures of the Polycomb Group complex components Pc, Sce, esc and H3K27me3 are highly similar. Other combinations of proteins are more surprising. For example, the BRICKs for Mnt, H3K4me2, Sin3A, and eve overlap strongly on chromosome 2L around ∼10 Mb (Fig. 4A). BRICKs of Lamin, His1, D1, and SuUR also overlap, between ∼14 and ∼18 Mb on chromosome 2L. Some proteins can be part of different types of domains: In pericentric regions, D1 shares BRICKs with HP1 and other heterochromatin components, but at other sites D1 is found in various combinations with Lam, SuUR and His1 (Supplementary Fig. S4). Similarly, Sin3A forms different combinations with Sir2, H3K4me2, and Mnt (Fig. 4A and Supplementary Fig. S4), and also with H3.3 and eve (with the caveat that the latter profiles were not obtained in the Kc167 cell line). These results are suggestive of a combinatorial “chromatin code” that marks specific domains.


Global chromatin domain organization of the Drosophila genome.

de Wit E, Braunschweig U, Greil F, Bussemaker HJ, van Steensel B - PLoS Genet. (2008)

BRICK locations for all tested proteins.A) BRICKs on chromosome arm 2L. BRICKs smaller than 100 probed genes are shown for all analyzed proteins. The proteins are ordered by hierarchical clustering, with proteins that have the strongest overlapping domains closest together in the figure. B) Combined overview of the BRICKs for all proteins on all chromosome arms. BRICKs of different proteins are color-coded as indicated. Vertical position corresponds to the number of genes contained in the BRICK. Note that a substantial part of the Drosophila genome (∼50%) is covered by at least one BRICK.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2274884&req=5

pgen-1000045-g004: BRICK locations for all tested proteins.A) BRICKs on chromosome arm 2L. BRICKs smaller than 100 probed genes are shown for all analyzed proteins. The proteins are ordered by hierarchical clustering, with proteins that have the strongest overlapping domains closest together in the figure. B) Combined overview of the BRICKs for all proteins on all chromosome arms. BRICKs of different proteins are color-coded as indicated. Vertical position corresponds to the number of genes contained in the BRICK. Note that a substantial part of the Drosophila genome (∼50%) is covered by at least one BRICK.
Mentions: To compare the spatial binding patterns of the 29 tested proteins and histone marks, we used a visual representation in which their respective BRICKs are stacked, providing a compact simultaneous view of their chromosomal domain structure (Fig. 4A and Supplementary Fig. S4). This revealed that several proteins have strongly overlapping BRICKs, suggesting that these proteins may act together to form a distinct chromatin domain. As expected, heterochromatin components HP1, Su(var)3-9, HP3/Lhr, HP4, HP5 and HP6 colocalize in BRICKS in pericentric regions (Supplementary Fig. S4) and can also be seen to form a small consistent domain at position ∼8 Mb on chromosome 2L (Fig. 4A). Likewise, the BRICK structures of the Polycomb Group complex components Pc, Sce, esc and H3K27me3 are highly similar. Other combinations of proteins are more surprising. For example, the BRICKs for Mnt, H3K4me2, Sin3A, and eve overlap strongly on chromosome 2L around ∼10 Mb (Fig. 4A). BRICKs of Lamin, His1, D1, and SuUR also overlap, between ∼14 and ∼18 Mb on chromosome 2L. Some proteins can be part of different types of domains: In pericentric regions, D1 shares BRICKs with HP1 and other heterochromatin components, but at other sites D1 is found in various combinations with Lam, SuUR and His1 (Supplementary Fig. S4). Similarly, Sin3A forms different combinations with Sir2, H3K4me2, and Mnt (Fig. 4A and Supplementary Fig. S4), and also with H3.3 and eve (with the caveat that the latter profiles were not obtained in the Kc167 cell line). These results are suggestive of a combinatorial “chromatin code” that marks specific domains.

Bottom Line: Furthermore, during evolution fewer chromosomal rearrangements occur inside chromatin domains than outside domains.Our results indicate that a substantial portion of the Drosophila genome is packaged into functionally coherent, multi-gene chromatin domains.This has broad mechanistic implications for gene regulation and genome evolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

ABSTRACT
In eukaryotes, neighboring genes can be packaged together in specific chromatin structures that ensure their coordinated expression. Examples of such multi-gene chromatin domains are well-documented, but a global view of the chromatin organization of eukaryotic genomes is lacking. To systematically identify multi-gene chromatin domains, we constructed a compendium of genome-scale binding maps for a broad panel of chromatin-associated proteins in Drosophila melanogaster. Next, we computationally analyzed this compendium for evidence of multi-gene chromatin domains using a novel statistical segmentation algorithm. We find that at least 50% of all fly genes are organized into chromatin domains, which often consist of dozens of genes. The domains are characterized by various known and novel combinations of chromatin proteins. The genes in many of the domains are coregulated during development and tend to have similar biological functions. Furthermore, during evolution fewer chromosomal rearrangements occur inside chromatin domains than outside domains. Our results indicate that a substantial portion of the Drosophila genome is packaged into functionally coherent, multi-gene chromatin domains. This has broad mechanistic implications for gene regulation and genome evolution.

Show MeSH
Related in: MedlinePlus