Abstract: The present invention provides compositions, methods, and kits for generating and isolating tagged nuclei of specific cell types with a high yield and purity. The compositions, methods, and kits provided herein comprise expressing in a cell a nuclear envelope tagging fusion polypeptide comprising a nuclear envelope targeting domain and an affinity reagent binding region. In some embodiments, expression of the fusion polypeptide is under the control of a cell type-specific promoter. Some embodiments also comprise expressing in a cell a biotin ligase, wherein the affinity reagent binding region comprises a biotin ligase accepting site, and wherein at least one of the nuclear envelope tagging fusion polypeptide and the biotin ligase is expressed under the control of a cell type-specific promoter.