Dataset Information

Mapping active promoters by ChIP-seq profiling of H3K4me3 in cichlid fish - a first step to uncover cis-regulatory elements in ecological model teleosts

ABSTRACT: Evolutionary alterations to cis-regulatory sequences are likely to cause adaptive phenotypic complexity, through orchestrating changes in cellular proliferation, identity and communication. For non-model organisms with adaptive key-innovations, patterns of regulatory evolution have been predominantly limited to targeted sequence-based analyses. Chromatin-immunoprecipitation with high-throughput sequencing (ChIP-seq) is a technology that has only been used in genetic model systems and is a powerful experimental tool to screen for active cis-regulatory elements. Here, we show that it can also be used in ecological model systems and permits genome-wide functional exploration of cis-regulatory elements. As a proof of concept, we use ChIP-seq technology in adult fin tissue of the cichlid fish Oreochromis niloticus to map active promoter elements, as indicated by occupancy of trimethylated Histone H3 Lysine 4 (H3K4me3). The fact that cichlids are one of the most phenotypically diverse and species-rich families of vertebrates could make them a perfect model system for the further in-depth analysis of the evolution of transcriptional regulation.

ORGANISM(S): Oreochromis niloticus

PROVIDER: GSE62791 | GEO | 2015/07/07

SECONDARY ACCESSION(S): PRJNA265129

REPOSITORIES: GEO

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Project description:Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects on gene expression are due to nearby genetic variants, trans effects are due to distal genetic variants that affect diffusible elements such as transcription factors. However, as previous studies have mostly assessed the impacts of cis and trans effects at the gene level, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we used massively parallel reporter assays to directly measure cis and trans effects between human and mouse embryonic stem cells at thousands of individual regulatory elements, including enhancers as well as promoters of both protein-coding and long non-coding RNA genes. Our approach revealed that cis effects are widespread across regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we found that trans effects are rare but stronger in enhancers than promoters, and can be attributed to a subset of transcription factors that are differentially expressed between human and mouse. While previous gene-based studies have found extensive co-occurrence of cis and trans effects in opposite directions that stabilize gene expression between species—or compensatory cis-trans effects—we find that cis-trans compensation is uncommon within individual regulatory elements. Moreover, regulatory elements that do show compensatory cis-trans effects are often less redundant than regulatory elements lacking compensatory cis-trans effects. Thus, our results are consistent with a model wherein compensatory cis-trans effects occur more often through crosstalk between multiple redundant regulatory elements than within a single individual regulatory element. Together, these results indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.

Dataset Information

Mapping active promoters by ChIP-seq profiling of H3K4me3 in cichlid fish - a first step to uncover cis-regulatory elements in ecological model teleosts

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