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Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes.

Ganapathi M, Srivastava P, Das Sutar SK, Kumar K, Dasgupta D, Pal Singh G, Brahmachari V, Brahmachari SK - BMC Bioinformatics (2005)

Bottom Line: The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression.The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression.This could partially explain the lower number of genes estimated in the human genome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi-110007, India. mythilyg@igib.res.in

ABSTRACT

Background: Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group.

Results: In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes.

Conclusion: The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

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A model for chromatin landscape in 5' regions of tissue specific and housekeeping genes. (A) depicts the repressive role of chromatin in maintaining tissue specific gene expression profiles in a chromosome. The chromatin organisation in the 5' regions of Tsg1 and Tsg2, two different tissue specific genes dispersed in the chromosome is shown. Nucleosome formation potentials and S/MARs – the boundary elements, are enriched in their upstream regions and might play a major role in facilitating tissue specific expression. This is likely to be a local effect since neighbouring genes might have a different expression pattern. (B) depicts the chromatin organisation in the 5' regions of Hkg1, Hkg2 and Hkg3, three housekeeping genes clustered in the chromosome. The presence of low nucleosome formation potential regions and enrichment of nucleosome destabilising elements ensure an open chromatin configuration in this domain. As Hkg generally cluster together, they are depleted in S/MARs relative to tissue specific genes as shown in the present analysis by the significant absence of predicted S/MARs in both 5' and 3' regions of housekeeping genes as compared to tissue specific genes.
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Figure 3: A model for chromatin landscape in 5' regions of tissue specific and housekeeping genes. (A) depicts the repressive role of chromatin in maintaining tissue specific gene expression profiles in a chromosome. The chromatin organisation in the 5' regions of Tsg1 and Tsg2, two different tissue specific genes dispersed in the chromosome is shown. Nucleosome formation potentials and S/MARs – the boundary elements, are enriched in their upstream regions and might play a major role in facilitating tissue specific expression. This is likely to be a local effect since neighbouring genes might have a different expression pattern. (B) depicts the chromatin organisation in the 5' regions of Hkg1, Hkg2 and Hkg3, three housekeeping genes clustered in the chromosome. The presence of low nucleosome formation potential regions and enrichment of nucleosome destabilising elements ensure an open chromatin configuration in this domain. As Hkg generally cluster together, they are depleted in S/MARs relative to tissue specific genes as shown in the present analysis by the significant absence of predicted S/MARs in both 5' and 3' regions of housekeeping genes as compared to tissue specific genes.

Mentions: The paradigm for regulation of gene expression in human tissues has shifted the focus from involvement of a battery of transcription regulators to global regulatory mechanisms [31]. These mechanisms have also gained significance in the context of the low estimates of gene numbers in the human genome [32]. It is in this framework that we have analysed the chromatin characteristics of two groups of genes, one that needs almost a continuous and ubiquitous expression and another demanding tissue specific regulation. It had been predicted that the nucleosomal density in a chromatin domain and the buffering of supercoiling waves by repetitive DNA will play a major role in establishing coordinated gene regulation in a domain in the context of the relevance of maintenance of repetitive sequences during evolution [[25,33], and [34]]. A recent report also infers the role of chromatin-mediated mechanisms in the differential gene expression patterns seen in housekeeping and tissue specific genes [29]. Our data and analyses lend support to these hypotheses (Figure 3). Another recent report, which addresses the chromatin architecture of the human genome, provides experimental evidence that open chromatin correlates with high gene density regions but not with gene expression [35]. This data further supports our in-silico observations and strengthens the domain concept for concerted expression of clustered genes. The role of nucleosome formation potential is apparent from the present analysis in both the housekeeping genes as well as tissue specific genes but with an opposing correlation. Housekeeping genes apparently discourage nucleosome formation to match their expression profile in space and time by ensuring accessibility to transcription machinery. In addition, they also show a significant enrichment in poly (dA.dT) stretches, which are known to destabilise nucleosomes. On the other hand, the tissue specific genes show higher scores for nucleosome formation potential through which they perhaps provide selective accessibility to the transcriptional machinery. Further, our analysis suggests that tissue specific genes resort to additional global regulatory features such as matrix association, which would facilitate maintenance of functionally distinct domains to insulate themselves from both silencing and activating regulatory influence of adjacent domains. The differential distribution of repetitive sequences in housekeeping and tissue specific genes might also play an important role in maintaining distinct chromatin landscape over these regions.


Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes.

Ganapathi M, Srivastava P, Das Sutar SK, Kumar K, Dasgupta D, Pal Singh G, Brahmachari V, Brahmachari SK - BMC Bioinformatics (2005)

A model for chromatin landscape in 5' regions of tissue specific and housekeeping genes. (A) depicts the repressive role of chromatin in maintaining tissue specific gene expression profiles in a chromosome. The chromatin organisation in the 5' regions of Tsg1 and Tsg2, two different tissue specific genes dispersed in the chromosome is shown. Nucleosome formation potentials and S/MARs – the boundary elements, are enriched in their upstream regions and might play a major role in facilitating tissue specific expression. This is likely to be a local effect since neighbouring genes might have a different expression pattern. (B) depicts the chromatin organisation in the 5' regions of Hkg1, Hkg2 and Hkg3, three housekeeping genes clustered in the chromosome. The presence of low nucleosome formation potential regions and enrichment of nucleosome destabilising elements ensure an open chromatin configuration in this domain. As Hkg generally cluster together, they are depleted in S/MARs relative to tissue specific genes as shown in the present analysis by the significant absence of predicted S/MARs in both 5' and 3' regions of housekeeping genes as compared to tissue specific genes.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC1173084&req=5

Figure 3: A model for chromatin landscape in 5' regions of tissue specific and housekeeping genes. (A) depicts the repressive role of chromatin in maintaining tissue specific gene expression profiles in a chromosome. The chromatin organisation in the 5' regions of Tsg1 and Tsg2, two different tissue specific genes dispersed in the chromosome is shown. Nucleosome formation potentials and S/MARs – the boundary elements, are enriched in their upstream regions and might play a major role in facilitating tissue specific expression. This is likely to be a local effect since neighbouring genes might have a different expression pattern. (B) depicts the chromatin organisation in the 5' regions of Hkg1, Hkg2 and Hkg3, three housekeeping genes clustered in the chromosome. The presence of low nucleosome formation potential regions and enrichment of nucleosome destabilising elements ensure an open chromatin configuration in this domain. As Hkg generally cluster together, they are depleted in S/MARs relative to tissue specific genes as shown in the present analysis by the significant absence of predicted S/MARs in both 5' and 3' regions of housekeeping genes as compared to tissue specific genes.
Mentions: The paradigm for regulation of gene expression in human tissues has shifted the focus from involvement of a battery of transcription regulators to global regulatory mechanisms [31]. These mechanisms have also gained significance in the context of the low estimates of gene numbers in the human genome [32]. It is in this framework that we have analysed the chromatin characteristics of two groups of genes, one that needs almost a continuous and ubiquitous expression and another demanding tissue specific regulation. It had been predicted that the nucleosomal density in a chromatin domain and the buffering of supercoiling waves by repetitive DNA will play a major role in establishing coordinated gene regulation in a domain in the context of the relevance of maintenance of repetitive sequences during evolution [[25,33], and [34]]. A recent report also infers the role of chromatin-mediated mechanisms in the differential gene expression patterns seen in housekeeping and tissue specific genes [29]. Our data and analyses lend support to these hypotheses (Figure 3). Another recent report, which addresses the chromatin architecture of the human genome, provides experimental evidence that open chromatin correlates with high gene density regions but not with gene expression [35]. This data further supports our in-silico observations and strengthens the domain concept for concerted expression of clustered genes. The role of nucleosome formation potential is apparent from the present analysis in both the housekeeping genes as well as tissue specific genes but with an opposing correlation. Housekeeping genes apparently discourage nucleosome formation to match their expression profile in space and time by ensuring accessibility to transcription machinery. In addition, they also show a significant enrichment in poly (dA.dT) stretches, which are known to destabilise nucleosomes. On the other hand, the tissue specific genes show higher scores for nucleosome formation potential through which they perhaps provide selective accessibility to the transcriptional machinery. Further, our analysis suggests that tissue specific genes resort to additional global regulatory features such as matrix association, which would facilitate maintenance of functionally distinct domains to insulate themselves from both silencing and activating regulatory influence of adjacent domains. The differential distribution of repetitive sequences in housekeeping and tissue specific genes might also play an important role in maintaining distinct chromatin landscape over these regions.

Bottom Line: The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression.The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression.This could partially explain the lower number of genes estimated in the human genome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi-110007, India. mythilyg@igib.res.in

ABSTRACT

Background: Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group.

Results: In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes.

Conclusion: The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

Show MeSH
Related in: MedlinePlus