A gene transcribed from the bidirectional ATM promoter coding for a serine rich protein: amino acid sequence, structure and expression studies

Abstract

In an earlier report we showed that the 5' end of the gene for ataxia telangiectasia ATM is within 700 bp of the 5' end of a novel gene E14, and suggested that the CpG island that separates these genes functions as a bidirectional promoter. We have now determined the complete amino acid sequence of the E14 protein, defined the exon/intron structure of the gene and estimate that the complete gene is more than 55 kb in length. The E14 gene appears to be a housekeeping gene that is expressed in all tissues, including all parts of the brain. The E14/ATM promoter organisation is conserved in man, monkey and mouse, although the mouse promoter is more compact and appears to lack two of the four putative Sp1 boxes found in the human promoter. Reporter gene constructs showed that the human and mouse E14/ATM promoters were indeed bidirectional, that the ATM side of the human promoter was three times stronger than the E14 side, and that the mouse promoter (in human cells) directed transcription with equal efficiency in both directions, but at a lower level than the human promoter. Analysis of a small number of A-T patients for mutations in the promoter region or the E14 coding sequence did not provide evidence to suggest that E14 contributes to the A-T phenotype.

Expression of NPAT, a novel substrate of cyclin E-CDK2, promotes S-phase entry

“…2A) is not clear at present, but it could be the product of a differentially spliced NPAT mRNA or the product of a related gene. Consistent with this notion, two mRNA species that hybridize to the NPAT sequence have been detected in all human adult tissues examined and in several human cell lines (Byrd et al 1996;Imai et al 1996;Chen et al 1997; data not shown). The intensity of the band that migrates faster than the CDK2 band ( Fig.…”

“…Therefore, this clone was chosen for further studies. While our work was in progress, the gene was also isolated independently, under the names NPAT, E14, and CAN3, through positional cloning by virtue of the fact that the gene is located next to ATM on chromosome 11q22-q23 and may share a bidirectional promoter with ATM (Byrd et al 1996;Imai et al 1996;Chen et al 1997).…”

X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts

“…Thus, for example, the ATM sequence is organized in head-to-head configuration with the sequence of a second gene, NPAT/E14/CAND3, with which it shares a bi-directional promoter that contains CCAAT boxes and 4 consensus sites for the Sp1 transcription factor and whose transcription start site is only 550 base pairs away from the ATM start site. [28][29][30] Sp1 is a candidate factor for common regulation of the activities of these two genes. Additional evidence that may be of some relevance includes a recent report by Gueven et al 31) which indicates that epidermal growth factor (EGF) increases radiosensitivity in both human fibroblasts and lymphoblasts and that this is associated with a controlled down-regulation of ATM.…”

Systematic Analysis of Head-to-head Gene Organization: Evolutionary Conservation and Potential Biological Relevance

“…This gene organization was first observed in the investigation of mouse DHFR gene [3]. Subsequently, SURF-1/SURF-2 [4], COL4A1/COL4A2 [1], RanBP1/Htf9-c [5], E14/ATM [6], BRCA1/NBR2 [7], DNA-PKcs/MCM4 [8], FEN1/C11orf10 [9], and so on were identified in human, hamster, rat, or mouse through individual experiments. Of them, many cases, such as DHFR/REP3 [10], SURF-1/SURF-2 [11], E14/ATM [6], and TK/ KF [12], were found to be conserved among mammalian species.…”

“…Subsequently, SURF-1/SURF-2 [4], COL4A1/COL4A2 [1], RanBP1/Htf9-c [5], E14/ATM [6], BRCA1/NBR2 [7], DNA-PKcs/MCM4 [8], FEN1/C11orf10 [9], and so on were identified in human, hamster, rat, or mouse through individual experiments. Of them, many cases, such as DHFR/REP3 [10], SURF-1/SURF-2 [11], E14/ATM [6], and TK/ KF [12], were found to be conserved among mammalian species. Computational analysis revealed that more than 10% of human genes were organized in this head-to-head manner separated by less than 1,000 base pairs (bp), suggesting that bidirectional gene organization seems to be a common architectural feature of the human genome [2,9].…”