This region encompasses the 5\' regulatory region of SOX2 (SRY-box 2) and includes the proximal promoter and SOX2 regulatory region 1 (SRR1), which is a conserved enhancer. This sequence is positively regulated by binding of high mobility group AT-hook 1 and 2 and NK6 homeobox 3, and may be suppressed by msh homeobox 2, Y-box binding protein 1, and the polycomb complex. This promoter may be methylated and silenced in tumor cells. Four subregions were validated as active enhancers by ChIP-STARR-seq in human embryonic stem cells, where three are associated with the OCT4 and/or NANOG transcription factors, and three are marked by the H3K27ac and H3K4me1 histone modifications. A subregion of the SRR1 sequence was also validated as a functional repressive element by Sharpr-MPRA (Systematic high-resolution activation and repression profiling with reporter tiling using massively parallel reporter assays) in HepG2 liver carcinoma cells (group: HepG2 Repressive non-DNase unmatched - State 22:ReprW, weaker Polycomb repression). This locus also includes an accessible chromatin subregion that was validated as a silencer based on its 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]