No abstract

The interleukin-2 receptor alpha (IL-2R alpha) chain gene contains a sequence similar to the immunoglobulin (Ig) kappa (kappa) enhancer NF-kappa B binding site. This site, which is bound by the nuclear protein, NF-kappa B, is critical for Ig kappa gene expression. The major T cell nuclear factor that binds to the IL-2R alpha site in vitro appears indistinguishable from NF-kappa B. NF-kappa B binds to IL-2R alpha and kappa sequences with similar affinities; however, only the kappa site potently activates transcription from heterologous promoters. Thus, high-affinity NF-kappa B binding in vitro cannot be equated with transcriptional activation in vivo. Mutation of the NF-kappa B binding site in the context of an IL-2 R alpha promoter construct markedly diminished promoter activity in human T cell lymphotropic virus type I (HTLV-I)-transformed MT-2 cells but not in phorbol myristate acetate-stimulated Jurkat T cells.

The haploid genome of Saccharomyces cerevisiae contains two nonallelic sets of histone H3 and H4 gene pairs, termed the copy I and copy I loci. The structures of the mRNA transcripts from each of these four genes were examined by nuclease protection and primer extension mapping. For each gene, several species of mRNAs were identified that differed in the lengths of their S' and 3' untranslated regions. The cell cycle accumulation pattern of the H3 and H4 mRNAs was determined in cells from early-exponential-growth cultures fractionated by centrifugal elutriation. The RNA trnscripts from all four genes were regulated with the cell division cycle, and btanscripts from the nonallelic gene copies showed tight temporal coordination. Cell cycle regulation did not depend on selection of a particular histone mRNA transcript since the ratio of the multiple species from each gene remained the same across the division cycle. Quantitative measurements showed significant differences in the amounts of mRNA expressed from the two nonallelic gene sets. The mRNAs from the copy 11 H3 and H4 genes were five to seven times more abundant than the mRNAs from the copy I genes. There was no dosage compensation in the steady-state levels of mRNA when either set of genes was deleted. In particular, there was no increase in the amount of copy I H3 or H4 transcripts in cells in which the high-abundance copy II genes were deleted.For most classes of histone, gene expression is regulated in a cell-cycle-dependent fashion, with the maximal amount of histone RNA and protein synthesis occurring in late G1 or early S phase (28, 37). The replacement or basal histone gene variants (49) and avian histone H5 (7) are notable exceptions to this rule. The cell cycle regulation of histone mRNA expression has been investigated in several systems and is likely to involve changes in the rate of gene transcription (14,17,32), changes in mRNA stability (15,17,40), and structural features of the mRNA transcripts and their templates (4, 25).The core histone genes of budding yeast, Saccharomyces cerevisiae, are organized as duplicate H2A-H2B and H3-H4 gene pairs (43). The four nonallelic chromosomal gene sets are unlinked and, at each locus, the paired genes are divergently transcribed (19, 45). The DNA sequences of analogous genes are highly conserved within the coding regions, but the 5' and 3' untranslated regions are divergent. The yeast core histone genes show a typical cell-divisioncycle-dependent pattern of expression. Both the rate of synthesis of new histone (23, 24) and the appearance of histone mRNA are periodic in the division cycle (20). There appear to be several mechanisms regulating expression of the genes, and both transcriptional and posttranscriptional controls have been proposed for the H2A and H2B genes (18,26,32,33).In this paper, we report the structure and cell cycle pattern of accumulation of the yeast histone H3 and H4 genes. These experiments addressed several aspects of H3 and H4 gene expression. First, we determined the structures of...

The addition of lidocaine substantially reduces the pain of LGP-HA injection without altering safety. LGP-HA and LGP-HA+L were generally well tolerated in all Fitzpatrick skin types.