RT Journal Article
SR Electronic
T1 Mapping the micro-proteome of the nuclear lamina and lamina-associated domains
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000774
DO 10.26508/lsa.202000774
VO 4
IS 5
A1 Xianrong Wong
A1 Jevon A Cutler
A1 Victoria E Hoskins
A1 Molly Gordon
A1 Anil K Madugundu
A1 Akhilesh Pandey
A1 Karen L Reddy
YR 2021
UL https://www.life-science-alliance.org/content/4/5/e202000774.abstract
AB The nuclear lamina is a proteinaceous network of filaments that provide both structural and gene regulatory functions by tethering proteins and large domains of DNA, the so-called lamina-associated domains (LADs), to the periphery of the nucleus. LADs are a large fraction of the mammalian genome that are repressed, in part, by their association to the nuclear periphery. The genesis and maintenance of LADs is poorly understood as are the proteins that participate in these functions. In an effort to identify proteins that reside at the nuclear periphery and potentially interact with LADs, we have taken a two-pronged approach. First, we have undertaken an interactome analysis of the inner nuclear membrane bound LAP2β to further characterize the nuclear lamina proteome. To accomplish this, we have leveraged the BioID system, which previously has been successfully used to characterize the nuclear lamina proteome. Second, we have established a system to identify proteins that bind to LADs by developing a chromatin-directed BioID system. We combined the BioID system with the m6A-tracer system which binds to LADs in live cells to identify both LAD proximal and nuclear lamina proteins. In combining these datasets, we have further characterized the protein network at the nuclear lamina, identified putative LAD proximal proteins and found several proteins that appear to interface with both micro-proteomes. Importantly, several proteins essential for LAD function, including heterochromatin regulating proteins related to H3K9 methylation, were identified in this study.