scholarly journals DNA sequences required for regulated expression of β-globin genes in murine erythroleukaemia cells

1984 ◽  
Vol 307 (1132) ◽  
pp. 271-282 ◽  
Keyword(s):  
Translation Initiation ◽  
Dna Sequences ◽  
Transcriptional Activation ◽  
Relative Rate ◽  
Globin Gene ◽  
Initiation Site ◽  
Translation Initiation Site ◽  
Globin Genes ◽  
S1 Nuclease ◽  
Hybrid Genes

We have introduced into murine erythroleukaemia (MEL) cells a series of human globin gene cosmids and two sets of hybrid genes constructed from the human β-globin gene and the human γ-globin or m urine H-2K bml genes. S1-nuclease analysis of the mRNA products from these genes before and after MEL cell differentiation showed that the hum an β-globin gene, but not the human ε- or γ-globin or H-2K bml genes, is induced specifically. Hybrid genes containing hum an β-globin DNA sequences from either 5' or 3' side of the translation initiation site were both inducible. Measurement of the relative rate of transcription showed this induction to be the result of transcriptional activation. We therefore suggest that DNA sequences which regulate β-globin gene expression during MEL differentiation are located both 5' and 3' to the translation initiation site.

Class imbalance methods for translation initiation site recognition in DNA sequences

2012 ◽  
Vol 25 (1) ◽  
pp. 22-34 ◽  
Author(s):  
Nicolás García-Pedrajas ◽  
Javier Pérez-Rodríguez ◽  
María García-Pedrajas ◽  
Domingo Ortiz-Boyer ◽  
Colin Fyfe
Keyword(s):  
Translation Initiation ◽  
Dna Sequences ◽  
Class Imbalance ◽  
Initiation Site ◽  
Translation Initiation Site ◽  
Site Recognition

scholarly journals Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms

2006 ◽  
Vol 128 (1) ◽  
pp. 133-145 ◽  
Author(s):  
Rocio K. Finol-Urdaneta ◽  
Nina Strüver ◽  
Heinrich Terlau
Keyword(s):  
Translation Initiation ◽  
Cell Function ◽  
Functional Divergence ◽  
Initiation Site ◽  
Translation Initiation Site ◽  
Inactivation Kinetics ◽  
Mouse Heart ◽  
Redox Stress ◽  
Redox Modulation ◽  
Stress States

Ion channels are membrane-spanning proteins that allow ions to permeate at high rates. The kinetic characteristics of the channels present in a cell determine the cell signaling profile and therefore cell function in many different physiological processes. We found that Kv1.7 channels from mouse heart muscle have two putative translation initiation start sites that generate two channel isoforms with different functional characteristics, mKv1.7L (489 aa) and a shorter mKv1.7S (457 aa). The electrophysiological analysis of mKv1.7L and mKv1.7S channels revealed that the two channel isoforms have different inactivation kinetics. The channel resulting from the longer protein (L) inactivates faster than the shorter channels (S). Our data supports the hypothesis that mKv1.7L channels inactivate predominantly due to an N-type related mechanism, which is impaired in the mKv1.7S form. Furthermore, only the longer version mKv1.7L is regulated by the cell redox state, whereas the shorter form mKv1.7S is not. Thus, expression starting at each translation initiation site results in significant functional divergence. Our data suggest that the redox modulation of mKv1.7L may occur through a site in the cytoplasmic N-terminal domain that seems to encompass a metal coordination motif resembling those found in many redox-sensitive proteins. The mRNA expression profile and redox modulation of mKv1.7 kinetics identify these channels as molecular entities of potential importance in cellular redox-stress states such as hypoxia.

The coordinate replication of the human beta-globin gene domain reflects its transcriptional activity and nuclease hypersensitivity

1988 ◽  
Vol 8 (11) ◽  
pp. 4958-4965
Author(s):  
V Dhar ◽  
D Mager ◽  
A Iqbal ◽  
C L Schildkraut
Keyword(s):  
Cell Lines ◽  
Dna Sequences ◽  
Globin Gene ◽  
K562 Cells ◽  
Globin Genes ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Hypersensitive Sites ◽  
Flanking Sequences ◽  
Globin Gene Domain

The temporal order of replication of DNA sequences in the chromosomal domain containing the human beta-globin gene cluster and its flanking sequences (140 kilobases) was measured and compared in two different human cell lines. In human erythroleukemia (K562) cells, in which embryonic and fetal globin genes are transcribed, all of the sequences we examined from the beta-globin domain replicated early during S phase, while in HeLa cells, in which globin genes are transcriptionally silent, these sequences replicated late during S. Potential sites of initiation of DNA replication within this domain were identified. The beta-globin gene domain was also found to differ with respect to the nuclease sensitivity of the chromatin in these two cell lines. In K562 cells, hypersensitive sites for endogenous nucleases and DNase I were present in the chromatin near the earliest-replicating segments in the beta-globin domain.

scholarly journals Link Between Short tandem Repeats and Translation Initiation Site Selection

2018 ◽  
Author(s):  
M Arabfard ◽  
K Kavousi ◽  
A Delbari ◽  
M Ohadi
Keyword(s):  
Amino Acids ◽  
Translation Initiation ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Initiation Site ◽  
Translation Initiation Site ◽  
Vertebrate Species ◽  
Protein Coding ◽  
Human Specific ◽  
Short Tandem

AbstractRecent work in yeast and humans suggest that evolutionary divergence in cis-regulatory sequences impact translation initiation sites (TISs). Cis-elements can also affect the efficacy and amount of protein synthesis. Despite their vast biological implication, the landscape and relevance of short tandem repeats (STRs)/microsatellites to the human protein-coding gene TISs remain largely unknown. Here we characterized the STR distribution at the 120 bp cDNA sequence upstream of all annotated human protein-coding gene TISs based on the Ensembl database. Furthermore, we performed a comparative genomics study of all annotated orthologous TIS-flanking sequences across 47 vertebrate species (755,956 transcripts), aimed at identifying human-specific STRs in this interval. We also hypothesized that STRs may be used as genetic codes for the initiation of translation. The initial five amino acid sequences (excluding the initial methionine) that were flanked by STRs in human were BLASTed against the initial orthologous five amino acids in other vertebrate species (2,025,817 pair-wise TIS comparisons) in order to compare the number of events in which human-specific and non-specific STRs occurred with homologous and non-homologous TISs (i.e. ≥50% and <50% similarity of the five amino acids). We characterized human-specific STRs and a bias of this compartment in comparison to the overall (human-specific and non-specific) distribution of STRs (Mann Whitney p=1.4 × 10−11). We also found significant enrichment of non-homologous TISs flanked by human-specific STRs (p<0.00001). In conclusion, our data indicate a link between STRs and TIS selection, which is supported by differential evolution of the human-specific STRs in the TIS upstream flanking sequence.AbbreviationscDNAComplementary DNACDSCoding DNA sequenceSTRShort Tandem RepeatTISTranslation Initiation SiteTSSTranscription Start Site

scholarly journals Acetylation of a Specific Promoter Nucleosome Accompanies Activation of the ɛ-Globin Gene by β-Globin Locus Control Region HS2

2001 ◽  
Vol 21 (4) ◽  
pp. 1155-1163 ◽  
Author(s):  
Chang-Yun Gui ◽  
Ann Dean
Keyword(s):  
Control Region ◽  
Dna Sequences ◽  
Transcriptional Activation ◽  
Trichostatin A ◽  
Globin Gene ◽  
Chromatin Modification ◽  
Locus Control Region ◽  
Micrococcal Nuclease ◽  
Nuclease Sensitivity

ABSTRACT On stably replicating episomes, transcriptional activation of the ɛ-globin promoter by the β-globin locus control region HS2 enhancer is correlated with an increase in nuclease sensitivity which is limited to the TATA-proximal nucleosome (N1). To elucidate what underlies this increase in nuclease sensitivity and the link between chromatin modification and gene expression, we examined the nucleoprotein composition and histone acetylation status of transcriptionally active and inactive promoters. Micrococcal nuclease digestion of active promoters in nuclei released few nucleosome-like nucleoprotein complexes containing N1 sequences in comparison to results with inactive promoters. We also observed that N1 DNA fragments from active promoters are of a subnucleosomal length. Nevertheless, chromatin immunoprecipitation experiments indicate that histones H3 and H4 are present on N1 sequences from active promoters, with H3 being dramatically hyperacetylated compared with that from inactive promoters and vector sequences. Strikingly, H3 in the adjacent upstream nucleosome (N2) does not appear to be differentially acetylated in active and inactive promoters, indicating that the nucleosome modification of the promoter that accompanies transactivation by HS2 is highly directed and specific. However, global acetylation of histones in vivo by trichostatin A did not activate transcription in the absence of HS2, suggesting that HS2 contributes additional activities necessary for transactivation. N1 sequences from active promoters also contain reduced levels of linker histone H1. The detection of a protected subnucleosomal sized N1 DNA fragment and the recovery of N1 DNA sequences in immunoprecipitations using anti-acetylated H3 and H4 antibodies argue that N1 is present, but in an altered conformation, in the active promoters.

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