Researchers have mapped the binding locations of over 400 different proteins on the yeast genome, providing the most thorough and high-resolution map of chromosome architecture and gene regulation to date.
Genomes regulate their genes to maintain homeostasis. They also adapt to rapidly changing environments in order to regain homeostasis. To achieve these tasks, it has been necessary for the genome to evolve constitutive and inducible gene control. However, whether these controls are fundamentally different at the molecular levels remains unclear.
Yeast cells can respond to changes in their environment by altering chromatin architectures to turn different genes on or off. In multicellular organisms, differences between cell types arise by regulation of gene sets that those cells are expressing. Deciphering the mechanisms that control this differential gene expression is important to understand responses to the environment, organismal development and also evolution.
In this paper, published in Nature, researchers used ChIP-Exo (an ultra-high-resolution version of ChIP-seq) to map genome-wide binding in Saccharomyces cerevisiae. They specifically selected target proteins on the basis of Gene Ontology (GO) annotations related to chromosomal function. In total, they collected 1,229 datasets on 791 targets, of which 400 targets had reproducibly significant data. The analysis revealed 21 unique protein assemblages that are repeatedly used across the yeast genome. The different proteins involved were specifically related to DNA replication, centromeres, subtelomeres, transposons and transcription by RNA polymerase.
The team also clustered colocalisation of targets into three clusters which corresponded to three major aspects of gene expression: promoter regulation, preinitiation complex assembly and transcriptome elongation. Interestingly, the team also found the absence of specific regulatory control signals at housekeeping genes. The traditional model of gene regulation involves transcription factors binding to specific DNA sequence to control the expression of nearby genes. However, the team found that the majority of genes in yeast did not adhere to this model.
Franklin Pugh, Professor of molecular biology and genetics at Cornell University, expressed:
“We were surprised to find that housekeeping genes lacked a protein-DNA architecture that would allow specific transcription factors to bind, which is the hallmark of inducible genes.
These genes just seem to need a general set of proteins that allow access to the DNA and its transcription without much need for regulation. Whether or not this pattern holds up in multicellular organisms like humans is yet to be seen. It’s a vastly more complex proposition, but like the sequencing of the yeast genome preceded the sequencing of the human genome, I’m sure we will eventually be able to see the regulatory architecture of the human genome at high resolution.”
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