Poster presentation
216
STUDY OF GENE EXPRESSION OF DNA AND HISTONE
METHYLATION AND DEMETHYLATION ENZYMES IN RAT
STOMACH CELLS
I.T. Yakubov, J. Yusufjanova
National University of Uzbekistan named after Mirzo Ulugbek, Tashkent,
e-mail: iskandar2014a@gmail.com
The study of new genes in gastric epithelial cells by transcriptomic methods makes it
possible to determine their functions and develop new methods for the diagnosis and
treatment of gastrointestinal diseases. Until now, the functions of about 10% of the
genes in the stomach cells remained unknown.
In
contrast to DNA mutations, epigenetic modifications are reversible and, hence,
suitable for pharmacological interventions. Reversible histone methylation is an
important process within epigenetic regulation, and the investigation
of its role in cancer
has led to the identification of lysine methyltransferases and demethylases as promising
targets for new anticancer drugs.
The aim of this work is to identify unknown genes in the rat stomach transcriptome
and to study the expression of genes of histone methylation and demethylation enzymes
in various organs and cells of the rat stomach.
In this work, the rat stomach transcriptome database was used, which were deposited
for public access to the Gene Expression Omnibus National Center for Biotechnology
Information database under access numbers GPL1439, GSM30415, GSM30416,
GSM30417, GSE3518, GSM80287, and GSM80288.
Earlier, using the method of analysis of oligonucleotide microchips, together with
scientists from the University of California at Los Angeles, more than 41,372 transcripts of rat
stomach cells were identified. Of these, the functions of 37,698 (91.12%)
transcripts were
known, and the functions of approximately 3,676 (9.88%) genes remained unknown. The
names and systematic numbers of 2725 genes from 3676 (74.13%) unknown transcripts in the
rat stomach transcriptome were identified using the stomach transcriptome database and the
BLAST-nucleotide program. At the same time, the names of 948 (25.87%) genes in remained
unknown. The identified genes were classified into several groups: various enzymes,
small and long non-coding RNAs, ribosomal and mitochondrial proteins,
zinc-binding
domain containing proteins, oncogenic proteins, receptors, cytoskeletal proteins, histone
methylation and demethylation enzymes, and others.
For the first time, we determined the gene expression levels of the following
enzymes: lysine demethylase 1B (Kdm1b), lysine demethylase 2A (Kdm2a), lysine
demethylase 4B (Kdm4b), methyltransferase-like 11B (Mettl11b),
RB-binding protein
5, histone lysine-methyltransferase complex subunits (Rbbp5), methylictose
dioxygenase 3 (Tet3). Different isoforms of lysine demethylase had different levels of
gene expression. Isoforms 1B and 4B showed the highest levels of gene expression
(8299±1493 and 7448±1266, respectively), while isoform 2a
showed lower levels of
expression (1543±200). The ratio of gene expression levels in highly purified parietal
and enterochromaffin-like cells did not actually change.
Further study of the expression of genes and proteins of the enzymes of methylation and
demethylation of rat gastric histones makes it possible to find out the functions of these
enzymes in the stomach in various pathologies of the gastrointestinal tract.