Alternative sites of transcription initiation upstream of the canonical cap site in human -γ-globin andβ-globin genes

Abstract

Using S1 mapping and primer extension analysis, we have identified a number of human kappa-globin and beta-globin 5' RNA termini originating in the 200 bp upstream of the canonical mRNA cap sites. Upstream initiation sites have previously been reported for the human epsilon-globin gene (4,5) and the present work indicates that this is a general feature of the human beta-type globin genes. We have attempted to identify features common to such sites between the three genes. One site 170 bp upstream of the major beta-globin cap site and a site 1400 bp upstream of the major epsilon-globin cap site are located near putative PolIII promoter sequences and may therefore be transcribed by this enzyme. Alternative initiation sites located 200 bp and 50-100 bp upstream of the epsilon-globin and kappa-globin cap sites respectively are located within S1 hypersensitive regions of chromatin.

Human papillomavirus type 8 contains cis-active positive and negative transcriptional control sequences

“…4. Sequence similarity between the HPV-8 HpaI-AluI fragment (positions 1 to 243) and silencer elements of different genes (Grindlay et al, 1984;Brand et al, 1985Brand et al, , 1987Lakshmikumaran et al, 1985;Laimins et al, 1986;Wu & Mounts, 1988;Burt et al, 1989;Cao et al, 1989;Pech et al, 1989). Uppercase letters designate identical nucleotides.…”

“…The line above the nucleotides marks the conserved 29 bp (see text). ~ stands for the upstream sequences of the human renin gene (Burt et al, 1989); fl for rat insulin 1 gene upstream sequences (Lakshmikumaran et al, 1985;Laimins et al, 1986); z for the PDGF-2 promoter silencer element (Pech et al, 1989); e for the human e-globin upstream sequences (Grindlay et al, 1984;Cao et al, 1989) and/t for the yeast HMR silencer (Brand et al, 1985(Brand et al, , 1987.…”

Negative regulation of the human epsilon-globin gene by transcriptional interference: role of an Alu repetitive element.

“…They correlate with DHS in the ly-globin and 0-globin genes (18) and are located upstream of the (-and a-globin genes (21; T. Rutherford, personal communication). They are also found associated with a number of well-documented regulatory elements, including the simian virus 40 (SV40) enhancer (11), the immunoglobulin heavy-chain gene enhancer (27), the thymidine kinase upstream regulatory element (24), the Xenopus ribosomal regulatory element (26), and the adenovirus ElA enhancer (28).…”

Discrete human dihydrofolate reductase gene transcripts present in polysomal RNA map with their 5' ends several hundred nucleotides upstream of the main mRNA start site.

“…Transcripts of relatively low abundance have previously been found to irnitiate at various positions upstream (170 to 4,500 bp) of the major transcription initiation site for the mouse ,-globin gene (17) and for the human P-globin gene (8,15), -y-globin gene (15), and s-globin gene (1,2). The upstream initiating transcripts of the human ,3-globin gene have been shown to be synthesized by RNA polymerase III (Pol III [8]); furthermore, at least one e-globin transcript originates in an Alu repeat (1), raising the possibility that it also is produced by Pol III, since Pol III can initiate transcription at Alu repeat sequences in vitro (13,14,16,23,28 that the transcripts starting at the upstream initiation sites are spliced identically to the major DHFR-specific RNAs, at least up to the 5'-end proximal portion of the third DHFR exon.…”