Abstract
SummaryLRWD1, also known as ORCA, is a nuclear protein functioning in multiple biological processes. Using its WD40 domain LRWD1 interacts with repressive histone marks and maintains the silencing of heterochromatin regions in mammalian cells. ORCA also associates with the origin recognition complex (ORC) and facilitates prereplication complex formation at late‐replicating origins. However, whether LRWD1 plays a role during development and the functional significance of LRWD1 in vivo remains largely unknown. Using gene‐trap approach we generated Lrwd1 knockout mice and examined the expression of Lrwd1 during embryonic development. We found that Lrwd1 is ubiquitously expressed in the majority of the developing mouse embryo. Depletion of LRWD1 did not affect embryonic development but the postnatal growth of the homozygous mutants is retarded. In vitro cultured mouse embryonic fibroblasts (MEFs) depleted of LRWD1 displayed a reduced proliferation compared to wild type cells. We also showed that the knockout of Lrwd1 in MEFs increased the expression of the epigenetically silenced repetitive elements but with minimal effect on the expression of protein coding genes. Together, these results suggest that LRWD1 plays an important, but not essential, role in postnatal development by regulating cell proliferation likely through modulating DNA replication.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.