Open Science Research Excellence
@article{(International Science Index):,
  title    = {Bioinformatic Analysis of Retroelement-Associated Sequences in Human and Mouse Promoters},
  author    = {Nadezhda M. Usmanova and  Nikolai V. Tomilin},
  country   = {},
  abstract  = {Mammalian genomes contain large number of
retroelements (SINEs, LINEs and LTRs) which could affect
expression of protein coding genes through associated transcription
factor binding sites (TFBS). Activity of the retroelement-associated
TFBS in many genes is confirmed experimentally but their global
functional impact remains unclear. Human SINEs (Alu repeats) and
mouse SINEs (B1 and B2 repeats) are known to be clustered in GCrich
gene rich genome segments consistent with the view that they
can contribute to regulation of gene expression. We have shown
earlier that Alu are involved in formation of cis-regulatory modules
(clusters of TFBS) in human promoters, and other authors reported
that Alu located near promoter CpG islands have an increased
frequency of CpG dinucleotides suggesting that these Alu are
undermethylated. Human Alu and mouse B1/B2 elements have an
internal bipartite promoter for RNA polymerase III containing
conserved sequence motif called B-box which can bind basal
transcription complex TFIIIC. It has been recently shown that TFIIIC
binding to B-box leads to formation of a boundary which limits
spread of repressive chromatin modifications in S. pombe. SINEassociated
B-boxes may have similar function but conservation of
TFIIIC binding sites in SINEs located near mammalian promoters
has not been studied earlier. Here we analysed abundance and
distribution of retroelements (SINEs, LINEs and LTRs) in annotated
sequences of the Database of mammalian transcription start sites
(DBTSS). Fractions of SINEs in human and mouse promoters are
slightly lower than in all genome but >40% of human and mouse
promoters contain Alu or B1/B2 elements within -1000 to +200 bp
interval relative to transcription start site (TSS). Most of these SINEs
is associated with distal segments of promoters (-1000 to -200 bp
relative to TSS) indicating that their insertion at distances >200 bp
upstream of TSS is tolerated during evolution. Distribution of SINEs
in promoters correlates negatively with the distribution of CpG
sequences. Using analysis of abundance of 12-mer motifs from the
B1 and Alu consensus sequences in genome and DBTSS it has been
confirmed that some subsegments of Alu and B1 elements are poorly
conserved which depends in part on the presence of CpG
dinucleotides. One of these CpG-containing subsegments in B1
elements overlaps with SINE-associated B-box and it shows better
conservation in DBTSS compared to genomic sequences. It has been
also studied conservation in DBTSS and genome of the B-box
containing segments of old (AluJ, AluS) and young (AluY) Alu
repeats and found that CpG sequence of the B-box of old Alu is
better conserved in DBTSS than in genome. This indicates that Bbox-
associated CpGs in promoters are better protected from
methylation and mutation than B-box-associated CpGs in genomic
SINEs. These results are consistent with the view that potential
TFIIIC binding motifs in SINEs associated with human and mouse
promoters may be functionally important. These motifs may protect
promoters from repressive histone modifications which spread from
adjacent sequences. This can potentially explain well known
clustering of SINEs in GC-rich gene rich genome compartments and
existence of unmethylated CpG islands.},
    journal   = {International Journal of Biological, Biomolecular, Agricultural, Food and Biotechnological Engineering},  volume    = {2},
  number    = {8},
  year      = {2008},
  pages     = {146 - 154},
  ee        = {},
  url       = {},
  bibsource = {},
  issn      = {eISSN:1307-6892},
  publisher = {World Academy of Science, Engineering and Technology},
  index     = {International Science Index 20, 2008},