Scientists at Indiana University have identified machinery of epigenetic inheritance, which is relevant to development and cancer. During the DNA sequences the scientists indentified the cells that don’t silence the genes. But those cells can recognize some heritable chemical marks that are added to the genes.
The molecular memory tags on chromatin help to acquire the gene silencing instructions. The chemical tags work as molecular memory that instructs the cells to recognize the genes and force them to remember to silence in every new generation. The epigenetic inheritance is the process by which the heritable modifications occur in gene function without changes in the base sequence of an organism’s DNA. Cancer is increasingly being recognized as having an epigenetic basis
The research work was organized by a 12-member all Indiana University team. The entire procedure was being led by IU biologist and biochemist Craig Pikaard. He is the person who has given the information about how a plant cell knows to silence the genetic locus. According to medical science the cells must remember the necessity of silencing the specific loci by relying on chemical marks displayed on the complex of DNA and proteins.
Craig Pikaard explained –“this work shows that silent locus identity is required for, but separable from, actual gene silencing. We’ve found that epigenetic inheritance is a two-step process, with the heritable specification of silent locus identity occurring before actual silencing of the locus can occur.” The work has shown that the silent locus identity is sustained through the generations after generations by the actions of HDA6 and MET1. But according to the research team this actions are not sufficient enough to adopt the silencing process but it retain a chromatin state that is required for Pol IV recruitment, siRNA biogenesis and RdDM, which is what ultimately silences the loci. The team removed the RdDM pathway in Pol IV and Pol V mutant strains from the model plant Arabidopsis thaliana (rockcress) and when they removed them they noticed that though the silent locus identity was still there but all the gene silencing was gone. The RNA polymerases Pol IV and Pol V are called gene silencing enzymes.
Pikkard first identified these two enzymes as the plant specific gene-silencing enzymes, in 1999. The new work also focuses new light on the mechanism responsible for epigenetic inheritance. The team tested and identified the relationship between histone deacetylase 6 (HDA6), an enzyme that removes acetyl groups from histones, and the CG DNA sequence maintenance methyltransferase, MET1, and discovered that their partnership in maintenance methylation can explain the perpetuation of epigenetic memory that accounts for silent locus identity.
The newest genetic research has shown that genetic testing may improve the treatment options for the women, who are suffering from ER+ breast cancer. Professor Mitch Dowsett announced the news about this medication discovery ate the 9th European Breast Cancer Conference in Glasgow. According to him, the women suffering from ER+ breast cancer may benefit by having ten years of hormone therapy instead of five years to prevent the disease recurring.
Hormone Therapy is that systematic therapy that helps to lower the growth level and prevents breast cancer from spreading cancer cells by altering hormone levels in body. Sometimes drugs or radio therapy s used for changing the levels. Precisely, Doctors does not prescribe for hormone therapy if the patient is having hormone receptor-negative tumor.
The genetic analyses have been run over 1125 postmenopausal women, who were being treated for oestrogen responsive breast cancer. The analyses have shown that some of those women were more likely to have a late recurrence of the cancer. Prof Mitch Dowsett also explained –“Our data suggest that these patients, who are those that appear to benefit most from the current standard five years of endocrine treatment, may also benefit from adjuvant hormone treatment that extends beyond that five years.
HER2-negative tumors that are very sensitive to oestrogen are usually considered to be relatively low risk, yet these were the tumors that showed an increase in recurrence after five years, which coincided with the cessation of adjuvant hormonal therapy”. And that was why this factor doubled the chance of having the cancer recurring between five and ten years after surgery. The ATAC trial team was investigating the benefit of hormone therapy in ER positive breast cancer post-surgery patients. The team has noticed that some of the patients were having the chances of developing recurrent cancer but some of the women were more likely to be protected. The ATAC trial team is testing 900 tumors for identifying the oestrogen-sensitive tumors better than by the genes in the Oncotype test.
The team believes that this trial also help them to gather the knowledge of creating better predictors of recurrence both for the first five years and subsequent years after diagnosis. Professor Giuseppe Viale, chair of EBCC-9 and Head of the Department of Pathology at the University of Milan said – “these latest findings from the ATAC trial may pave the way for a better tailoring of hormone therapy beyond the first five years. Certainly, confirmatory studies are needed, and it remains to be assessed whether the same prognostic parameters may also hold for pre-menopausal patients.”
Latest discovery on genetic research reveals that genetic disorder causes strokes and vascular inflammation in children. A team from NIH (National Institutes of Health) has identified the gene variants, which are responsible for these health deformities. According to NIH, the gene variants cause a rare syndrome of sporadic fevers, recurring strokes and skin rashes that begin early in childhood. A research held by Israeli team has also identified an overlapping set of variants of the same gene in patients with a similar type of blood vessel inflammation.
10 years back, NIH faced a patient, who had been suffering from fever, skin rashes and several strokes. The patient was then only 3 years old. NIH had not faced similar syndrome before, so they took it as immunosuppressant and the begun to treat accordingly. But 2years back the NIH team again has been reported about a 6year old patient suffering from similar syndrome as the previous child. The second child has changed the team’s view and they begun suspecting it as a common genetic cause which finally reveals the fundamental new insight into the genes. In the advance online edition of the New England Journal of Medicine released on 19th Feb, 2014, NIH reported that they found that harmful variants in the CECR1 gene impede production of a protein vital to the integrity of healthy blood vessel walls. Eric D. Green, M.D., Ph.D., director of the NHGRI (National Human Genome Research Institute) said –”This discovery is another example of genome sequencing playing a central role in revealing the genomic basis for an important rare disease. Such studies illustrate how genomics is paving the way to improved human health.”
The Team has explained that the DNA, which are responsible for encoding CECR1 gene, promote the loss of functions of the gene’s ability to produce ADA2 (adenosine deaminase 2) enzyme. The lack of this enzyme causes the abnormalities and inflammation in blood vessel walls. The researcher called it –“the deficiency ADA2 or DADA2”. The research was led by Manfred Boehm, who is the M.D., senior investigator at the National Heart, Lung, and Blood Institute. He first established the link between ADA2 deficiency and inflammatory blood vessel disease in the patients. Dan Yang, (M.D., Ph.D., a staff scientist in Dr. Boehm’s lab), who has discovered that ADA2 deficiency causes a faulty function in a subset of white blood cells called monocytes, has explained that the discovery of the molecular basis of DADA2 has treatment implications. The joined hand research held by NHGRI and NIH would definitely be a forward step toward future genetic engineering and medications.