In this work, we have analyzed at blastocyst stage the expression of some genes that are modifiers of
epigenetic gene silencing that produce considerable variance in many complex traits in inbred individuals reared in controlled environments [39, 40].
We have found that blastocysts produced by suboptimal IVC exhibit transcriptional repression of some genes (Sox2, Hdac1, Kap1, Dnmt1, and Dnmt3a) that are modifiers of
epigenetic gene silencing through the regulation of the transcription of specific genes, which involves changes in the chromatin state.
This result suggests that the mechanism by which IVC alters phenotype could be related to mechanisms of
epigenetic gene silencing.
Interestingly, it has been reported that reduced levels of two modifiers of
epigenetic gene silencing, Dnmt3a and Kap1, cause an increased phenotypic noise, suggesting that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation [43].
We are interested in dissecting the mechanisms of
epigenetic gene silencing and understanding the functional relevance of DNA methylation in diseases.
Reduced levels of two modifiers of
epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise
We are focusing on a few key molecular pathways including; 1) Polycomb - mediated
epigenetic gene silencing in the tumor initiation, maintenance, and invasion, 2) c - Met (receptor tyrosine kinase) signal transduction pathways in stemness and migration of these tumor cells, 3) Novel mitogenic signaling pathways that are specific to GSCs, and 4) Identification of radio - and chemo - sensitizing pathway to maximize therapeutic efficacy.
Not exact matches
Epigenetics involves the study of the circumstances that cause
genes to be activated or
silenced.
Medical research focusing on
epigenetics is currently trying to block the enzymes that regulate these changes thereby
silencing cancer promoting
genes.
Epigenetics refers to how certain life circumstances can cause
genes to be
silenced or expressed, become dormant or active, over time.
Most research on
epigenetics has focused on the way everyday experiences alter patterns of
gene activity in DNA during life through a chemical process of
gene tagging called methylation, which usually
silences genes.
The researchers treated 63 cancer cell lines (26 breast, 14 colorectal and 23 ovarian) with low - dose 5 - azacitidine (AZA), an FDA - approved drug for myelodysplastic syndrome, that reverses
epigenetic changes by stripping off the methyl group that
silences the
gene.
Gore and her colleagues believe these effects are
epigenetic; that is, rather than inducing genetic mutations, which would change the sequence of the rats» DNA, the fungicide is permanently
silencing or reprogramming normal
genes that control development and behavior.
Much of the previous research on
epigenetics has focused on the fact that everyday experiences alter patterns of
gene activity in DNA during life through a chemical process of
gene tagging called methylation, which usually
silences genes.
Hypermethylation of DNA is a key
epigenetic mechanism for the
silencing of many
genes, including those for cell cycle regulation, receptors, DNA repair, and apoptosis (5, 6, 7, 8).
Amabile A, Migliara A, Capasso P, Biffi M, Naldini L, Lombardo A. Inheritable
silencing of endogenous
genes by hit - and - run targeted
epigenetic editing.
In these cases, it looks like the
genes are being
silenced at inappropriate times by
epigenetic changes.
Epigenetics began as a correlative field in which covalent modifications to DNA or histones, the proteins that help package DNA, were associated with
gene expression or
silencing.
This happens by
epigenetic silencing of the other copy, where specific marks on the DNA carry a memory of whether a
gene sitting on a copy of a chromosome came from the sperm or the egg.
Thus, another form of
epigenetics provided compensatory
gene silencing.
These two histones thus have a key role of
epigenetic silencing of tumor suppressor
genes in breast cancer (and likely other cancers), suggesting that they may represent new therapeutic targets.
The scientists also found that the
genes that do not carry either of the two
epigenetic modifications are completely
silenced in ES cells.
ONE - PARENT SAMPLE SET PARENTAL GUIDANCE RULES: Maternally methylated (red dots) and paternally methylated (blue dots) regions across the human autosomal chromosomes, based on studies of uniparental disomy samplesGENOME RES, 24:554 - 69, 2014 RESEARCHERS Kazuhiko Nakabayashi, Division Chief, Department of Maternal - Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan; David Monk, Principal Investigator,
Epigenetics and Cancer Biology Program, Bellvitge Institute for Biomedical Research ORGANISM Human METHODS Bisulfite - seq; bisulfite - chip Methylation is typically associated with the
silencing of the nonexpressed allele, making it a convenient marker for imprinted
genes, though it's possible for patterns of differential methylation to exist in tissues where both alleles are expressed.
Epigenetics Dream Team leaders have identified an
epigenetic process, known as DNA de-methylation, that inactivates or «
silences» key
genes that might otherwise correct for the «mistakes» that permit cancer to exist and flourish.
Her graduate work culminated in multiple publications in the field of cancer
epigenetics and in a thesis entitled «Aberrant
epigenetic silencing of tumor suppressor
genes in human cancer: the roles of DNA hypermethylation and the histone code.»
The relative amount of mRNA of 11
genes related to
epigenetic reprogramming and
gene silencing was quantified in blastocysts produced in vivo or produced in vitro in KSOM media supplemented with FCS (suboptimal condition) or with BSA (optimal condition).
Here, through a genome - wide CRISPR - Cas9 - mediated forward genetic screen, we identified MORC2 as an essential
gene required for
epigenetic silencing by the HUSH complex.
Finally, we analyzed, through
gene silencing, the effect of IVC on the mRNA expression at the blastocyst stage for 11 known
gene expression modifiers of
epigenetic reprogramming.
Since IGF2R is imprinted (i.e. one copy of the
gene silenced by DNA methylation), this finding thrusted me into the rapidly growing research field of
epigenetics.
Conclusion: some babies are getting off to a bum start in life due to
epigenetic silencing of an important
gene.
Many phytochemicals can reactivate tumor suppressor
genes silenced by
epigenetic modifications.