دانلود رایگان ترجمه مقاله پروموتورهای دوطرفه در رونویسی از ژنوم پستانداران (نشریه اسپرینگر ۲۰۱۳)

پروموتورهای دوطرفه در رونویسی از ژنوم پستانداران

Bidirectional Promoters in the Transcription of Mammalian Genomes

Abstract

In the genomes of humans and other mammals a large number of closely spaced pairs of genes that are transcribed in opposite directions were revealed. Their transcription is directed by so
called bidirectional promoters. This review is devoted to the characteristics of bidirectional promoters and features of their structure. The composition of “core” promoter elements in conventional unidirectional and bidirectional promoters is compared. Data on binding sites of transcription fac
tors that are primarily specific for bidirectional promoters are discussed. The examples of promoters that share protein
cod
ing genes transcribed by RNA polymerase II and the non
coding RNA genes transcribed by RNA polymerase III are described. Data obtained from global transcriptome analysis about the existence of short noncoding antisense RNA associ
ated with the promoters in the context of the hypothesis of bidirectional transcription initiation as an inherent property of eukaryotic promoters are discussed.

The genomes of higher eukaryotes are excessive, and an important place in them is engaged by non
coding sequences. Many protein
coding genes have very extend
ed 5′ regulatory regions that contain alternate promoters, often separated by tens of thousands of nucleotides. Despite this redundancy in genomes of humans and other mammals there are a large number of closely spaced, ori
ented head
to
head and transcribed in opposite direc
tions pairs of genes. Such gene pairs are separated by small intergenic region of less than one thousand base pairs (kb) length, which have a bidirectional promoter activity. This review covers the current understanding of the prevalence of bidirectional promoters in the genomes of mammals, peculiar properties of their organization and functioning, and of the transcription factors, binding sites of which are overrepresented in bidirectional promoters. In the final part of the review we discuss the hypothesis that the ability of bidirectional transcription initiation is an inherent property of eukaryotic promoters.

PREVALENCE OF BIDIRECTIONAL PROMOTERS IN MAMMALIAN GENOMES

Decoding of the nucleotide sequence of the human genome has opened the possibility for global analysis of gene organization. Already in early such studies, it was shown that tightly linked pairs of genes oriented head to head make up a very substantial fraction of the protein
coding genes [1, 2]. In particular, it was found that 31 of the 144 genes of chromosome 21, i.e. 22%, are located in the head
to
head orientation and are separated by spacers less than 1 kb [1]. A similar ratio (56 genes with such ori
entation of 319 (18%)) was found in chromosome 22 [1]. The search for such pairs of genes based on full
length cDNA mapping of the human genome showed slightly lower figures. Analysis of the distances between 23,752 genes showed that more than 10% of protein
coding genes of humans are transcribed from bidirectional pro
moters [2, 3]. In papers of Koyanagi et al. [4] and Frank et al. [5] it was shown that the enrichment of closely located bidirectional pairs of genes characteristic for the mammalian genome is less pronounced in other verte
brates. Prediction of bidirectional promoters in the genomes of humans and mammals was successfully per
formed using bioinformatic methods [6
۸]. The study of features of mouse gene expression that are transcribed from bidirectional promoters by hybridization to microarrays showed that very often the genes transcribed in opposite directions from one bidirectional promoter are coordinately regulated [9]. The activities of bidirec
tional promoters in four different cell lines were defined, and it was found that the efficiency of transcription in opposite directions can be controlled to some extent depending on the cell type [2]. Thus, mammalian genomes contain a large number of bidirectional promot
ers directing transcription of closely oriented head
to
head gene pairs.