ABSTRACT
Metazoan development requires the robust proliferation of progenitor cells, the identities of which are established by tightly controlled transcriptional networks1. As gene expression is globally inhibited during mitosis, the transcriptional programs that define cell identity must be restarted in each cell cycle2-5 but how this is accomplished is poorly understood. Here we identify a ubiquitin-dependent mechanism that integrates gene expression with cell division to preserve cell identity. We found that WDR5 and TBP, which bind active interphase promoters6,7, recruit the anaphase-promoting complex (APC/C) to specific transcription start sites during mitosis. This allows APC/C to decorate histones with ubiquitin chains branched at Lys11 and Lys48 (K11/K48-branched ubiquitin chains) that recruit p97 (also known as VCP) and the proteasome, which ensures the rapid expression of pluripotency genes in the next cell cycle. Mitotic exit and the re-initiation of transcription are thus controlled by a single regulator (APC/C), which provides a robust mechanism for maintaining cell identity throughout cell division.
Subject(s)
Anaphase-Promoting Complex-Cyclosome/metabolism , Cell Differentiation/genetics , Gene Expression Regulation , Multiprotein Complexes/metabolism , Anaphase , Cell Division , HEK293 Cells , HeLa Cells , Histones/chemistry , Histones/metabolism , Human Embryonic Stem Cells/cytology , Human Embryonic Stem Cells/metabolism , Humans , Interphase , Intracellular Signaling Peptides and Proteins/metabolism , Mitosis , Organophosphates/metabolism , Polyubiquitin/metabolism , Proteasome Endopeptidase Complex/metabolism , Transcription Initiation Site , Ubiquitin/metabolism , UbiquitinationABSTRACT
Korean Americans (KA) face a significant burden of health disparities. However, limited data are available on their health needs. This health needs assessment includes a community-based sample of 342 KA from the San Francisco Bay Area. The assessment investigated participants' sociodemographic characteristics, health status, and their healthcare needs. Nearly half of the survey participants rated their health as fair or poor, > 30% did not have a usual place for healthcare, and chronic conditions were prevalent. Limited English Proficiency (LEP) was significantly associated with low self-rated health and having no usual source of care, after adjusting for other sociodemographic factors. Older, LEP KA faced the highest health and health care burden. In addition, females were less likely to be physically active. Males were more likely to smoke. The findings provide guidance in identifying major KA health needs and supports local programming and policy development for KA.
