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.