H19 regulatory locus (H19 locus)

The H19 regulatory locus is a critical genomic region on chromosome 11 that controls the expression of the H19 long non-coding RNA (lncRNA) and the insulin-like growth factor 2 (IGF2) gene through genomic imprinting. This locus includes the H19 promoter and the imprinting control region (ICR), which are regulated by epigenetic factors, including DNA methylation and the binding of linker histones like Histone H1. Specifically, Histone H1.3 has been identified as a direct repressor of the H19 locus, where its binding promotes a condensed chromatin state and increases DNA methylation to silence H19 expression. In various malignancies, such as bladder, ovarian, and pancreatic cancers, the H19 locus becomes dysregulated, leading to the overexpression of the H19 lncRNA, which functions as an oncogene by promoting cell proliferation, epithelial-mesenchymal transition, and resistance to chemotherapy. Therapeutic strategies targeting this locus include the use of the H19 promoter to drive the expression of cytotoxic genes (e.g., BC-819/DTA-H19) specifically in cancer cells, as well as small molecules and antisense oligonucleotides designed to modulate H19 levels.

Other names

H19/IGF2 imprinting control regionH19 promoterH19 imprinting control regionH19 ICRH19-IGF2 locus

Transcriptional activation of diphtheria toxin A gene; Modulation of lncRNA expression; Epigenetic silencing