Transcriptional regulation of Ligase IV by an intronic regulatory element directs thymocyte development.

ABSTRACT: Double-strand breaks represent the most dangerous form of DNA damage, and in resting cells, these breaks are sealed via the non-homologous end joining (NHEJ) factor Ligase IV (LIG4). Excessive NHEJ may be genotoxic, necessitating multiple mechanisms to control NHEJ activity. However, a clear mechanism of transcriptional control for them has not yet been identified. Here, we examine mechanisms governing Lig4 transcription in mammals, finding that most tissues maintain very low levels of LIG4 production. Select tissues upregulate LIG4, employing different strategies for genomic regulation. In developing lymphocytes, the Lig4 locus is devoid of long-range chromatin contacts; instead, its expression and role in immune development depend upon a promoter-proximal intronic regulatory element. Del

SUBMITTER: Estrada MD 

PROVIDER: S-EPMC12527937 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature