DNA polymerase α interacts with H3-H4 and facilitates the transfer of parental histones to lagging strands.
Sci Adv
; 6(35): eabb5820, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32923642
ABSTRACT
How parental histones, the carriers of epigenetic modifications, are deposited onto replicating DNA remains poorly understood. Here, we describe the eSPAN method (enrichment and sequencing of protein-associated nascent DNA) in mouse embryonic stem (ES) cells and use it to detect histone deposition onto replicating DNA strands with a relatively small number of cells. We show that DNA polymerase α (Pol α), which synthesizes short primers for DNA synthesis, binds histone H3-H4 preferentially. A Pol α mutant defective in histone binding in vitro impairs the transfer of parental H3-H4 to lagging strands in both yeast and mouse ES cells. Last, dysregulation of both coding genes and noncoding endogenous retroviruses is detected in mutant ES cells defective in parental histone transfer. Together, we report an efficient eSPAN method for analysis of DNA replication-linked processes in mouse ES cells and reveal the mechanism of Pol α in parental histone transfer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Histonas
/
DNA Polimerase I
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article