要約
This region represents the promoter and associated regulatory elements of the cytochrome P450 family 1 subfamily A member 1 (CYP1A1) gene. This promoter is stimulated by aromatic hydrocarbons and other xenobiotics, which are thought to trigger binding of aryl hydrocarbon receptor to multiple recognition elements in this sequence. This promoter is also regulated through binding of retinoic X receptor to discrete sites, where it forms dimers with transcriptional regulators such as peroxisome proliferator activated receptor alpha, nuclear receptor subfamily 1 members, or vitamin D receptor to promote gene expression. Ascorbic acid, estrogen, and hydrogen peroxide downregulate promoter activity. A subregion was validated as an active enhancer by the STARR-seq (self-transcribing active regulatory region sequencing) massively parallel reporter assay (MPRA) in HCT116 colorectal carcinoma cells, where it was defined as a group 4 enhancer that depends on the BRD2, P300/CBP, MED14 and CDK7 cofactors, but it has limited or no dependence on the BRD4 bromodomain protein. Sequence elements in this genomic region may function bidirectionally to regulate the adjacent CYP1A2 gene, located approximately 23 kb upstream in the opposite orientation. This locus also includes two accessible chromatin subregions that were validated as silencers based on their ability to repress 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]