title: A subset of replication-dependent histone mRNAs are expressed as polyadenylated RNAs in terminally differentiated tissues.
abstract: Histone proteins are synthesized in large amounts during S-phase to package the newly replicated DNA, and are among the most stable proteins in the cell. The replication-dependent (RD)-histone mRNAs expressed during S-phase end in a conserved stem-loop rather than a polyA tail. In addition, there are replication-independent (RI)-histone genes that encode histone variants as polyadenylated mRNAs. Most variants have specific functions in chromatin, but H3.3 also serves as a replacement histone for damaged histones in long-lived terminally differentiated cells. There are no reported replacement histone genes for histones H2A, H2B or H4. We report that a subset of RD-histone genes are expressed in terminally differentiated tissues as polyadenylated mRNAs, likely serving as replacement histone genes in long-lived non-dividing cells. Expression of two genes, HIST2H2AA3 and HIST1H2BC, is conserved in mammals. They are expressed as polyadenylated mRNAs in fibroblasts differentiated in vitro, but not in serum starved fibroblasts, suggesting that their expression is part of the terminal differentiation program. There are two histone H4 genes and an H3 gene that encode mRNAs that are polyadenylated and expressed at 5- to 10-fold lower levels than the mRNAs from H2A and H2B genes, which may be replacement genes for the H3.1 and H4 proteins.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Lyons
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Clark H
authors.initials: CH
authors.lastname: Cunningham
authors.affiliation: Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Welch
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Beezly
authors.initials: B
authors.lastname: Groh
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Guo
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Wei
authors.affiliation: Department of Genetics, Dartmouth Geisel School of Medicine, Hanover, NH 03755, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Whitfield
authors.affiliation: Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599.|Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA marzluff@med.unc.edu.|Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599.|Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Marzluff
mesh_terms: D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D015870:Gene Expression; D006657:Histones / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity / Q000235:genetics; D011061:Poly A; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D012333:RNA, Messenger; D011061:Poly A