Phosphorylated Lamin A/C in the Nuclear Interior Binds Active Enhancers Associated with Abnormal Transcription in Progeria.

08:00 EDT 23rd March 2020 | BioPortfolio

Summary of "Phosphorylated Lamin A/C in the Nuclear Interior Binds Active Enhancers Associated with Abnormal Transcription in Progeria."

LMNA encodes nuclear Lamin A/C that tethers lamina-associated domains (LADs) to the nuclear periphery. Mutations in LMNA cause degenerative disorders including the premature aging disorder Hutchinson-Gilford progeria, but the mechanisms are unknown. We report that Ser22-phosphorylated (pS22) Lamin A/C was localized to the nuclear interior in human fibroblasts throughout the cell cycle. pS22-Lamin A/C interacted with a subset of putative active enhancers, not LADs, at locations co-bound by the transcriptional activator c-Jun. In progeria-patient fibroblasts, a subset of pS22-Lamin A/C-binding sites were lost, whereas new pS22-Lamin A/C-binding sites emerged in normally quiescent loci. New pS22-Lamin A/C binding was accompanied by increased histone acetylation, increased c-Jun binding, and upregulation of nearby genes implicated in progeria pathophysiology. These results suggest that Lamin A/C regulates gene expression by enhancer binding. Disruption of the gene regulatory rather than LAD tethering function of Lamin A/C may underlie the pathogenesis of disorders caused by LMNA mutations.


Journal Details

This article was published in the following journal.

Name: Developmental cell
ISSN: 1878-1551
Pages: 699-713.e11


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