HAND2 invades nucleolar condensates to pioneer lineage-specific cardiac pacemaker gene programs.

ABSTRACT: Although best known as the site for ribosome assembly, the nucleolus organizes heterochromatin into transcriptionally repressed Nucleolus-Associated Domains (NADs). NADs harbor many genes involved in cell-type specification, yet the mechanisms by which transcription factors (TFs) access this heterochromatin to activate gene expression remain unknown. Using a model of TF-induced cardiac pacemaker reprogramming, we conclusively establish that nucleolar localization of HAND2 is required for successful lineage conversion. Moreover, we perform unbiased transcriptional profiling to demonstrate that pacemaker gene programs are highly compartmentalized within the nucleus. Finally, we show that HAND2 homodimers invade nucleolar condensates and concentrate within the nucleolus to bind palindromic mo

SUBMITTER: Kulkarni K 

PROVIDER: S-EPMC12514281 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature