Dataset Information

Coding region structural heterogeneity and turnover of transcription start sites contribute to divergence in expression between duplicate genes.

ABSTRACT:

Background

Gene expression divergence is one manifestation of functional differences between duplicate genes. Although rapid accumulation of expression divergence between duplicate gene copies has been observed, the driving mechanisms behind this phenomenon have not been explored in detail.

Results

We examine which factors influence expression divergence between human duplicate genes, utilizing the latest genome-wide data sets. We conclude that the turnover of transcription start sites between duplicate genes occurs rapidly after gene duplication and that gene pairs with shared transcription start sites have significantly higher expression similarity than those without shared transcription start sites. Moreover, we find that most (55%) duplicate gene pairs do not retain the same coding sequence structure between the two duplicate copies and this also contributes to divergence in their expression. Furthermore, the proportion of aligned sequences in cis-regulatory regions between the two copies is positively correlated with expression similarity. Surprisingly, we find no effect of copy-specific transposable element insertions on the divergence of duplicate gene expression.

Conclusions

Our results suggest that turnover of transcription start sites, structural heterogeneity of coding sequences, and divergence of cis-regulatory regions between copies play a pivotal role in determining the expression divergence of duplicate genes.

SUBMITTER: Park C

PROVIDER: S-EPMC2687787 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Coding region structural heterogeneity and turnover of transcription start sites contribute to divergence in expression between duplicate genes.

Park Chungoo C Makova Kateryna D KD

Genome biology 20090128 1

<h4>Background</h4>Gene expression divergence is one manifestation of functional differences between duplicate genes. Although rapid accumulation of expression divergence between duplicate gene copies has been observed, the driving mechanisms behind this phenomenon have not been explored in detail.<h4>Results</h4>We examine which factors influence expression divergence between human duplicate genes, utilizing the latest genome-wide data sets. We conclude that the turnover of transcription start ...[more]

PMID: 19175934

Similar Datasets

Project description:BackgroundMore than half of human protein-coding genes have an alternative transcription start site (TSS). We aimed to investigate the contribution of alternative TSSs to the acute-stress-induced transcriptome response in human tissue (skeletal muscle) using the cap analysis of gene expression approach. TSSs were examined at baseline and during recovery after acute stress (a cycling exercise).ResultsWe identified 44,680 CAGE TSS clusters (including 3764 first defined) belonging to 12,268 genes and annotated for the first time 290 TSSs belonging to 163 genes. The transcriptome dynamically changes during the first hours after acute stress; the change in the expression of 10% of genes was associated with the activation of alternative TSSs, indicating differential TSSs usage. The majority of the alternative TSSs do not increase proteome complexity suggesting that the function of thousands of alternative TSSs is associated with the fine regulation of mRNA isoform expression from a gene due to the transcription factor-specific activation of various alternative TSSs. We identified individual muscle promoter regions for each TSS using muscle open chromatin data (ATAC-seq and DNase-seq). Then, using the positional weight matrix approach we predicted time course activation of "classic" transcription factors involved in response of skeletal muscle to contractile activity, as well as diversity of less/un-investigated factors.ConclusionsTranscriptome response induced by acute stress related to activation of the alternative TSSs indicates that differential TSSs usage is an essential mechanism of fine regulation of gene response to stress stimulus. A comprehensive resource of accurate TSSs and individual promoter regions for each TSS in muscle was created. This resource together with the positional weight matrix approach can be used to accurate prediction of TFs in any gene(s) of interest involved in the response to various stimuli, interventions or pathological conditions in human skeletal muscle.

Project description:Cap Analysis of Gene Expression (CAGE) in combination with single-molecule sequencing technology allows precision mapping of transcription start sites (TSSs) and genome-wide capture of promoter activities in differentiated and steady state cell populations. Much less is known about whether TSS profiling can characterize diverse and non-steady state cell populations, such as the approximately 400 transitory and heterogeneous cell types that arise during ontogeny of vertebrate animals. To gain such insight, we used the chick model and performed CAGE-based TSS analysis on embryonic samples covering the full 3-week developmental period. In total, 31,863 robust TSS peaks (>1 tag per million [TPM]) were mapped to the latest chicken genome assembly, of which 34% to 46% were active in any given developmental stage. ZENBU, a web-based, open-source platform, was used for interactive data exploration. TSSs of genes critical for lineage differentiation could be precisely mapped and their activities tracked throughout development, suggesting that non-steady state and heterogeneous cell populations are amenable to CAGE-based transcriptional analysis. Our study also uncovered a large set of extremely stable housekeeping TSSs and many novel stage-specific ones. We furthermore demonstrated that TSS mapping could expedite motif-based promoter analysis for regulatory modules associated with stage-specific and housekeeping genes. Finally, using Brachyury as an example, we provide evidence that precise TSS mapping in combination with Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-on technology enables us, for the first time, to efficiently target endogenous avian genes for transcriptional activation. Taken together, our results represent the first report of genome-wide TSS mapping in birds and the first systematic developmental TSS analysis in any amniote species (birds and mammals). By facilitating promoter-based molecular analysis and genetic manipulation, our work also underscores the value of avian models in unravelling the complex regulatory mechanism of cell lineage specification during amniote development.

Dataset Information

Coding region structural heterogeneity and turnover of transcription start sites contribute to divergence in expression between duplicate genes.

Background

Results

Conclusions

Publications

Coding region structural heterogeneity and turnover of transcription start sites contribute to divergence in expression between duplicate genes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets