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Regional regulation of transcription in the bovine genome.

Kommadath A, Nie H, Groenen MA, te Pas MF, Veerkamp RF, Smits MA - PLoS ONE (2011)

Bottom Line: The objectives here were to provide evidence for the existence of chromosomal regional regulation of transcription in the bovine genome, to analyse the genomic features of genes located within RIDGEs versus anti-RIDGEs and tissue-specific genes versus housekeeping and to examine the genomic distribution of genes subject to positive selection in bovines.Housekeeping genes (defined here as genes expressed in all five tissues) were over-represented within RIDGEs but tissue-specific genes (genes expressed in only one of the five tissues) were not.Housekeeping genes and genes within RIDGEs had, in general, higher expression levels and GC content but shorter gene lengths and intron lengths than tissue-specific genes and genes within anti-RIDGES.

View Article: PubMed Central - PubMed

Affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, Lelystad, The Netherlands. arun.kommadath@wur.nl

ABSTRACT
Eukaryotic genes are distributed along chromosomes as clusters of highly expressed genes termed RIDGEs (Regions of IncreaseD Gene Expression) and lowly expressed genes termed anti-RIDGEs, interspersed among genes expressed at intermediate levels or not expressed. Previous studies based on this observation suggested a dual mechanism of gene regulation, where, in addition to transcription factors, the chromosomal domain influences the expression level of their embedded genes. The objectives here were to provide evidence for the existence of chromosomal regional regulation of transcription in the bovine genome, to analyse the genomic features of genes located within RIDGEs versus anti-RIDGEs and tissue-specific genes versus housekeeping and to examine the genomic distribution of genes subject to positive selection in bovines. Gene expression analysis of four brain tissues and the anterior pituitary of 28 cows identified 70 RIDGEs and 41 anti-RIDGEs (harbouring 3735 and 1793 bovine genes respectively) across the bovine genome which are significantly higher than expected by chance. Housekeeping genes (defined here as genes expressed in all five tissues) were over-represented within RIDGEs but tissue-specific genes (genes expressed in only one of the five tissues) were not. Housekeeping genes and genes within RIDGEs had, in general, higher expression levels and GC content but shorter gene lengths and intron lengths than tissue-specific genes and genes within anti-RIDGES. Our findings suggest the existence of chromosomal regional regulation of transcription in the bovine genome. The genomic features observed for genes within RIDGEs and housekeeping genes in bovines agree with previous studies in several other species further strengthening the hypothesis of selective pressure to keep the highly and widely expressed genes short and compact for transcriptional efficiency. Further, positively selected genes were found non-randomly distributed on the genome with a preference for RIDGEs and regions of intermediate gene expression compared to anti-RIDGEs.

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Determination of expressed genes and their tissue wise distribution.The blue line in the graph on the left represents expression levels of negative controls on the microarray and the red line represents that of all other probes. The 99.9% quantile value of expression levels of all negative controls across all arrays was 11.94, which was taken as the threshold above which a gene was considered as expressed. The graph on the right depicts the number of tissues in which the expressed genes are distributed and their tissue wise distributions. Here, ‘1’ represents the “tissue-specific” genes i.e. expressed only in one tissue (total of 1035), ‘2’ represents genes expressed in 2 tissues and so on. Number ‘5’ represents genes expressed in all five tissues which we defined here as “housekeeping” genes (total of 3651). (AP-Anterior Pituitary, AM-Amygdala, HC-Hippocampus, DH- Dorsal Hypothalamus, VH-Ventral Hypothalamus).
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pone-0020413-g005: Determination of expressed genes and their tissue wise distribution.The blue line in the graph on the left represents expression levels of negative controls on the microarray and the red line represents that of all other probes. The 99.9% quantile value of expression levels of all negative controls across all arrays was 11.94, which was taken as the threshold above which a gene was considered as expressed. The graph on the right depicts the number of tissues in which the expressed genes are distributed and their tissue wise distributions. Here, ‘1’ represents the “tissue-specific” genes i.e. expressed only in one tissue (total of 1035), ‘2’ represents genes expressed in 2 tissues and so on. Number ‘5’ represents genes expressed in all five tissues which we defined here as “housekeeping” genes (total of 3651). (AP-Anterior Pituitary, AM-Amygdala, HC-Hippocampus, DH- Dorsal Hypothalamus, VH-Ventral Hypothalamus).

Mentions: In order to define the threshold for expression, the normalized expression intensities of all genes and negative controls across all arrays and tissues was determined (Figure 5). The threshold for expression defined as the 99.9% quantile value of the log transformed expression levels of negative controls across all arrays, was 11.94. Figure 5 also shows the number of tissues in which the expressed genes are distributed, where ‘1’ represents the TS genes expressed only in one tissue (total of 1035 for the five tissues), ‘2’ represents genes expressed in 2 tissues and so on. Number ‘5’ represents genes expressed in all 5 tissues which we defined here as HK genes (total of 3651). The distribution of the 1035 TS genes across individual tissues is also shown (see Table S3 for list of HK and TS genes). The maximum number of TS genes was seen for the AP (490) which is an endocrine gland. The brain areas, being all of neurological tissue type, share a lot of functions in common and therefore genes. Hence the number of unique TS genes found were smaller (141 for AM, 102 for HC, 239 for DH, 63 for VH). Functional analysis of the orthologous human genes of the bovine genes (human orthologues used for better annotation information available) in R package ‘GOstats’ (see Materials and Methods) revealed enriched gene ontology and KEGG pathway terms for the HK and TS genes (Table S4). In most cases, the terms were not significant at a Benjamini-Hochberg p-value threshold of 0.1, hence the top 10–15 terms were considered to get an indication of the most important functions. Briefly, functional analysis of TS genes per tissue revealed processes like ‘negative regulation of synaptic transmission, glutamatergic’, ‘negative regulation of transmission of nerve impulse’ and ‘regulation of behaviour’ for the anterior pituitary, and processes like ‘androgen receptor signalling pathway’, ‘neurotransmitter catabolic process’, ‘behavioural response to pain’ for the brain areas. For HK genes, general processes related to ATP synthesis, mitotic activity and translation, typical of most tissues, were found to be enriched.


Regional regulation of transcription in the bovine genome.

Kommadath A, Nie H, Groenen MA, te Pas MF, Veerkamp RF, Smits MA - PLoS ONE (2011)

Determination of expressed genes and their tissue wise distribution.The blue line in the graph on the left represents expression levels of negative controls on the microarray and the red line represents that of all other probes. The 99.9% quantile value of expression levels of all negative controls across all arrays was 11.94, which was taken as the threshold above which a gene was considered as expressed. The graph on the right depicts the number of tissues in which the expressed genes are distributed and their tissue wise distributions. Here, ‘1’ represents the “tissue-specific” genes i.e. expressed only in one tissue (total of 1035), ‘2’ represents genes expressed in 2 tissues and so on. Number ‘5’ represents genes expressed in all five tissues which we defined here as “housekeeping” genes (total of 3651). (AP-Anterior Pituitary, AM-Amygdala, HC-Hippocampus, DH- Dorsal Hypothalamus, VH-Ventral Hypothalamus).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3108615&req=5

pone-0020413-g005: Determination of expressed genes and their tissue wise distribution.The blue line in the graph on the left represents expression levels of negative controls on the microarray and the red line represents that of all other probes. The 99.9% quantile value of expression levels of all negative controls across all arrays was 11.94, which was taken as the threshold above which a gene was considered as expressed. The graph on the right depicts the number of tissues in which the expressed genes are distributed and their tissue wise distributions. Here, ‘1’ represents the “tissue-specific” genes i.e. expressed only in one tissue (total of 1035), ‘2’ represents genes expressed in 2 tissues and so on. Number ‘5’ represents genes expressed in all five tissues which we defined here as “housekeeping” genes (total of 3651). (AP-Anterior Pituitary, AM-Amygdala, HC-Hippocampus, DH- Dorsal Hypothalamus, VH-Ventral Hypothalamus).
Mentions: In order to define the threshold for expression, the normalized expression intensities of all genes and negative controls across all arrays and tissues was determined (Figure 5). The threshold for expression defined as the 99.9% quantile value of the log transformed expression levels of negative controls across all arrays, was 11.94. Figure 5 also shows the number of tissues in which the expressed genes are distributed, where ‘1’ represents the TS genes expressed only in one tissue (total of 1035 for the five tissues), ‘2’ represents genes expressed in 2 tissues and so on. Number ‘5’ represents genes expressed in all 5 tissues which we defined here as HK genes (total of 3651). The distribution of the 1035 TS genes across individual tissues is also shown (see Table S3 for list of HK and TS genes). The maximum number of TS genes was seen for the AP (490) which is an endocrine gland. The brain areas, being all of neurological tissue type, share a lot of functions in common and therefore genes. Hence the number of unique TS genes found were smaller (141 for AM, 102 for HC, 239 for DH, 63 for VH). Functional analysis of the orthologous human genes of the bovine genes (human orthologues used for better annotation information available) in R package ‘GOstats’ (see Materials and Methods) revealed enriched gene ontology and KEGG pathway terms for the HK and TS genes (Table S4). In most cases, the terms were not significant at a Benjamini-Hochberg p-value threshold of 0.1, hence the top 10–15 terms were considered to get an indication of the most important functions. Briefly, functional analysis of TS genes per tissue revealed processes like ‘negative regulation of synaptic transmission, glutamatergic’, ‘negative regulation of transmission of nerve impulse’ and ‘regulation of behaviour’ for the anterior pituitary, and processes like ‘androgen receptor signalling pathway’, ‘neurotransmitter catabolic process’, ‘behavioural response to pain’ for the brain areas. For HK genes, general processes related to ATP synthesis, mitotic activity and translation, typical of most tissues, were found to be enriched.

Bottom Line: The objectives here were to provide evidence for the existence of chromosomal regional regulation of transcription in the bovine genome, to analyse the genomic features of genes located within RIDGEs versus anti-RIDGEs and tissue-specific genes versus housekeeping and to examine the genomic distribution of genes subject to positive selection in bovines.Housekeeping genes (defined here as genes expressed in all five tissues) were over-represented within RIDGEs but tissue-specific genes (genes expressed in only one of the five tissues) were not.Housekeeping genes and genes within RIDGEs had, in general, higher expression levels and GC content but shorter gene lengths and intron lengths than tissue-specific genes and genes within anti-RIDGES.

View Article: PubMed Central - PubMed

Affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, Lelystad, The Netherlands. arun.kommadath@wur.nl

ABSTRACT
Eukaryotic genes are distributed along chromosomes as clusters of highly expressed genes termed RIDGEs (Regions of IncreaseD Gene Expression) and lowly expressed genes termed anti-RIDGEs, interspersed among genes expressed at intermediate levels or not expressed. Previous studies based on this observation suggested a dual mechanism of gene regulation, where, in addition to transcription factors, the chromosomal domain influences the expression level of their embedded genes. The objectives here were to provide evidence for the existence of chromosomal regional regulation of transcription in the bovine genome, to analyse the genomic features of genes located within RIDGEs versus anti-RIDGEs and tissue-specific genes versus housekeeping and to examine the genomic distribution of genes subject to positive selection in bovines. Gene expression analysis of four brain tissues and the anterior pituitary of 28 cows identified 70 RIDGEs and 41 anti-RIDGEs (harbouring 3735 and 1793 bovine genes respectively) across the bovine genome which are significantly higher than expected by chance. Housekeeping genes (defined here as genes expressed in all five tissues) were over-represented within RIDGEs but tissue-specific genes (genes expressed in only one of the five tissues) were not. Housekeeping genes and genes within RIDGEs had, in general, higher expression levels and GC content but shorter gene lengths and intron lengths than tissue-specific genes and genes within anti-RIDGES. Our findings suggest the existence of chromosomal regional regulation of transcription in the bovine genome. The genomic features observed for genes within RIDGEs and housekeeping genes in bovines agree with previous studies in several other species further strengthening the hypothesis of selective pressure to keep the highly and widely expressed genes short and compact for transcriptional efficiency. Further, positively selected genes were found non-randomly distributed on the genome with a preference for RIDGEs and regions of intermediate gene expression compared to anti-RIDGEs.

Show MeSH
Related in: MedlinePlus