Dataset Information

Epigenetic characterization of housekeeping core promoters and their importance in tumor suppression.

ABSTRACT: In this research, we elucidate the presence of around 11,000 housekeeping cis-regulatory elements (HK-CREs) and describe their main characteristics. Besides the trivial promoters of housekeeping genes, most HK-CREs reside in promoter regions and are involved in a broader role beyond housekeeping gene regulation. HK-CREs are conserved regions rich in unmethylated CpG sites. Their distribution highly correlates with that of protein-coding genes, and they interact with many genes over long distances. We observed reduced activity of a subset of HK-CREs in diverse cancer subtypes due to aberrant methylation, particularly those located in chromosome 19 and associated with zinc finger genes. Further analysis of samples from 17 cancer subtypes showed a significantly increased survival probability of patients with higher expression of these genes, suggesting them as housekeeping tumor suppressor genes. Overall, our work unravels the presence of housekeeping CREs indispensable for the maintenance and stability of cells.

SUBMITTER: Loza M

PROVIDER: S-EPMC10853790 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epigenetic characterization of housekeeping core promoters and their importance in tumor suppression.

Loza Martin M Vandenbon Alexis A Nakai Kenta K

Nucleic acids research 20240201 3

In this research, we elucidate the presence of around 11,000 housekeeping cis-regulatory elements (HK-CREs) and describe their main characteristics. Besides the trivial promoters of housekeeping genes, most HK-CREs reside in promoter regions and are involved in a broader role beyond housekeeping gene regulation. HK-CREs are conserved regions rich in unmethylated CpG sites. Their distribution highly correlates with that of protein-coding genes, and they interact with many genes over long distance ...[more]

PMID: 38084904

Similar Datasets

Project description:Metazoan core promoters, which direct the initiation of transcription by RNA polymerase II (Pol II), may contain short sequence motifs termed core promoter elements/motifs (e.g. the TATA box, initiator (Inr) and downstream core promoter element (DPE)), which recruit Pol II via the general transcription machinery. The DPE was discovered and extensively characterized in Drosophila, where it is strictly dependent on both the presence of an Inr and the precise spacing from it. Since the Drosophila DPE is recognized by the human transcription machinery, it is most likely that some human promoters contain a downstream element that is similar, though not necessarily identical, to the Drosophila DPE. However, only a couple of human promoters were shown to contain a functional DPE, and attempts to computationally detect human DPE-containing promoters have mostly been unsuccessful. Using a newly-designed motif discovery strategy based on Expectation-Maximization probabilistic partitioning algorithms, we discovered preferred downstream positions (PDP) in human promoters that resemble the Drosophila DPE. Available chromatin accessibility footprints revealed that Drosophila and human Inr+DPE promoter classes are not only highly structured, but also similar to each other, particularly in the proximal downstream region. Clustering of the corresponding sequence motifs using a neighbor-joining algorithm strongly suggests that canonical Inr+DPE promoters could be common to metazoan species. Using reporter assays we demonstrate the contribution of the identified downstream positions to the function of multiple human promoters. Furthermore, we show that alteration of the spacing between the Inr and PDP by two nucleotides results in reduced promoter activity, suggesting a spacing dependency of the newly discovered human PDP on the Inr. Taken together, our strategy identified novel functional downstream positions within human core promoters, supporting the existence of DPE-like motifs in human promoters.

Dataset Information

Epigenetic characterization of housekeeping core promoters and their importance in tumor suppression.

Publications

Epigenetic characterization of housekeeping core promoters and their importance in tumor suppression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets