Nctc1 is a long non-coding RNA gene located within the Igf2-H19-Nctc1 locus. It is co-regulated with Igf2 and H19, and all three genes are associated with a shared muscle enhancer. This locus is crucial for studying monoallelic expression mechanisms and the role of cis-regulatory elements in chromatin organization and gene expression [2,3,4].

H19 lncRNA knockdown leads to increased DNMT3B-mediated methylation of Nctc1. This reveals an epigenetic regulatory circuit where H19 lncRNA, by modulating S-adenosylhomocysteine hydrolase (SAHH), influences the methylation of Nctc1, which may be related to gene methylation dynamics in development and diseases [1]. Also, promoter-promoter interactions via the shared enhancer explain the paternally biased expression of Nctc1, indicating a novel mechanism for its developmental-specific imprinting [3]. The insulin-like growth factor 2/H19 muscle enhancer requires transcription of Nctc1 in cis for its function, suggesting that this enhancer is an active transcriptional complex [4].

In conclusion, Nctc1 is integral to the regulatory network at the Igf2-H19 locus, with its methylation and expression being tightly regulated. Studies on Nctc1 contribute to understanding epigenetic regulation in development and potentially related disease mechanisms, especially those associated with abnormal gene methylation and imprinting [1,3,4].