HELLS: the transcriptional sentinel

The role of the chromatin remodeler HELicase Lymphoid Specific (HELLS) has been historically associated with DNA methylation and DNA damage repair. However, recent studies have shed light on an unexpected, multimodal, and direct participation of HELLS in transcriptional regulation. This forum article aims to discuss how, through different and context-specific mechanisms, HELLS modulates the expression of functionally related genes favoring transcriptional plasticity and phenotypic adaptation, ultimately safeguarding the genome organization and stability.