Summary
This genomic region represents the human ortholog of the mouse T helper type 2 (Th2) cytokine locus control region (LCR), which in transgenic assays can confer copy number-dependent, position-independent expression on the mouse interleukin 4 (Il4), interleukin 13 (Il13) and interleukin 5 (Il5) genes during differentiation of naive CD4+ T cells along the Th2 pathway. This region overlaps the 3\' end of the RAD50 gene, which is located between the IL13 and IL5 genes, and it also overlaps an opposite strand gene (TH2LCRR) that produces long non-coding RNAs. This region is characterized by three conserved DNase I hypersensitive sites (RHS5-RHS7), which bind transcription factors and are thought to regulate the IL4, IL5 and IL13 genes. The human RHS7 region has been shown to act as an enhancer, and it also includes a sub-fragment with silencing activity. RHS7 can affect expression of the RAD50 and IL4 genes, where the latter gene is relevant for the COVID-19 disease process. A polymorphism in RHS7 is associated with human atopic diseases, and it can affect protein binding and the regulatory potential of this element. A subregion was also validated as a silencer that could repress activity of a super core promoter (SCP1) by STARR-seq massively parallel reporter assays (MPRAs) in K562 erythroleukemia cells. This locus also includes two accessible chromatin subregions that were validated as enhancers based on their ability to activate an origin of replication minimal core promoter by the ATAC-STARR-seq (assay for transposase-accessible chromatin with self-transcribing active regulatory region sequencing) MPRA in GM12878 lymphoblastoid cells. [provided by RefSeq, May 2023] Annotation information: Note: This locus has been reviewed for its involvement in coronavirus biology, and is involved in host gene regulation.
