Replication-dependent histone gene expression is related to Cajal body (CB) association but does not require sustained CB contact

Interactions between Cajal bodies (CBs) and replication-dependent histone l oci occur more frequently than for other mRNA-encoding genes, but such inte ractions are not seen with all alleles at a given time. Because CBs contain factors required for transcriptional regulation and 3 ' end processing of nonpolyadenylated replication-dependent histone transcripts, we investigate d whether interaction with CBs is related to metabolism of these transcript s, known to vary during the cell cycle. Our experiments revealed that a loc us containing a cell cycle-independent, replacement histone gene that produ ces polyadenylated transcripts does not preferentially associate with CBs. Furthermore, modest but significant changes in association levels of CBs wi th replication-dependent histone loci mimic their cell cycle modulations in transcription and 3 ' end processing rates. By simultaneously visualizing replication-dependent histone genes and their nuclear transcripts for the f irst time, we surprisingly find that the vast majority of loci producing de tectable RNA foci do not contact CBs. These studies suggest some link betwe en CB association and unusual features of replication-dependent histone gen e expression. However, sustained CB contact is not a requirement for their expression, consistent with our observations of U7 snRNP distributions. The modest correlation to gene expression instead may reflect transient gene s ignaling or the nucleation of small CBs at gene loci.