Histone H1 variants differentially inhibit DNA replication through an affinity for chromatin mediated by their carboxyl-terminal domains.
Multiple forms of histone H1 are found in most mammalian tissues, and diversity in their temporal and spatial expression likely corresponds to diversity in function. Here, using Xenopus egg extracts, we show that while the somatic H1s significantly inhibit DNA replication in Xenopus sperm nuclei, little or no inhibition is seen in the case of the testes-specific variant, H1t. We suggest that differences in H1-chromatin interactions might explain some of the diversity in H1 function. To demonstrate this, we show that the somatic H1 variants preferentially assemble into chromatin relative to H1t. Differences in chromatin structure are seen depending on whether chromatin assembly occurs in the presence of somatic H1s or H1t. These data suggest that the mechanistic basis for some of the functional differences of H1 variants lies in their relative affinity for chromatin. Using a series of domain-switch mutants of H1(0) and H1t we identify the H1 carboxyl-terminal domains as the domains responsible for the differential affinity for chromatin and, concurrently, for the differential effects of H1 variants upon DNA replication.
Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Siddhartha
S
De
David T
DT
Brown
Zhi Hong
ZH
Lu
Gregory H
GH
Leno
Susan E
SE
Wellman
Donald B
DB
Sittman
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002457:Cell Extracts; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010063:Ovum / Q000187:drug effects / Q000378:metabolism; D014981:Xenopus
D002457:Cell Extracts; D002843:Chromatin; D006657:Histones