Lsh, a guardian of heterochromatin at repeat elements.

Lymphoid-specific helicase (Lsh) is a crucial factor for normal embryonic development; targeted deletion of Lsh is lethal. Lsh belongs to a family of chromatin-remodeling proteins and is closely associated with pericentromeric heterochromatin. Lsh deficiency leads to abnormal heterochromatin organization, with a loss of DNA methylation, and an altered pattern of histone-tail acetylation and methylation. As a functional consequence of perturbed heterochromatin, aberrant reactivation of parasitic retroviral elements in the genome and abnormal mitosis with amplified centrosomes and genomic instability were observed. Thus, Lsh is a major epigenetic regulator crucial for normal heterochromatin structure and function.