Multiple choice: how histone mods help choose where to splice

Humans can make about 100,000 different proteins with a mere 20,000 genes. How is this possible? The trick is in a process called alternative splicing, where the inclusion of different exons in mature mRNA allows the production of multiple proteins from a single gene.
The splicing machinery needs to recognise which exons to keep amongst the vast expanses of intronic sequences. So how does the splicing machinery choose where to do its job? A recent study by Luco and colleagues has proposed an answer and it involves histone modifications.
The researchers used an established model of alternative splicing, the human FGFR2 gene. The splicing that occurs in 2 different cell types leads to either exon IIIb or exon IIIc being included in the mRNA. They mapped the histone mods over the FGFR2 gene in both cell types and found that the amount of H3K36me3 was vastly increased in the cell type where exon IIIb is repressed. So the researchers tried to figure out how H3K36me3 affects the splicing outcome.
Their experiments led to the identification of a three part system made up of H3K36me3, a protein that binds to it, and the splicing regulator that represses exon IIIb.
Find out the fascinating details at http://www.sciencemag.org/cgi/content/abstract/327/5968/996

Astrid Vekemans 4239 6990

link between NNK and induces DNMT1

This study provides an explanation between the compounds found in cigarette or what is known as NNK ( nicotine ,nitrosamine and ketone) and the lung cancer, and what is the main causes to make NNK increase DNMT1 protein expression and activity? It also shed the light on over expression of DNMT1 protein stability through AKT signalling. It besides trigger off AKT then inhibits GSK3β/β-transducin repeat (include protein) mediated protein degradation, and the result DNMT1 protein accumulation.
It can be reason out that the conclusions made in this study are highly pertinent to the study of other Kind of cancer. It can be reason out that the conclusions made in this study are highly pertinent to the study of other Kind of cancer. The results showed assertions of this research provide an invaluable perspective in tumour and cancer research as well as studies on other types of human disease. It also opens up probability for developing better Means in improving prognosis in clinical manifestation of related epigenetic disorders that lead to these diseases.

Ahmad Baqazi

41606629

Review of induction of flowering by DNA demethylation in Perilla frutesencs and Silene armeria

YueLin LIU

42179054

The flowering process of many plants is regulated by gene expression, gene modification and/or environmental factors, such as temperature, night length and stress (K.C. Wada, et al, 2010). When talking about the gene modification, DNA methylation is always a crucial factor which is related to the plants’ vernalization. And also the methylation of DNA is a part of the epigenetic control. So in this research experiment, the authors focused on the cytidine analogue 5-azacytidine (azaC), which is commonly known as a methyltransferase inhibitor (C. Stresemann, et al, 2006), induced two kinds of plants, Perilla frutescens and Silene armeria, in order to find out the relationship between vernalization and DNA methylation and the heritability of the azaC induced effect in the offspring. What is more, they used methylation sensitive amplified fragment length polymorphism (MS-AFLP) analysis in these two plants so that the alterations of the DNA methylation states could be detected by changing the photoperiodic conditions.

Reference: Hiroshi Kondo, Takeshi Shiraya, Kaede C. Wada, Kiyotoshi Takeno. (2010). Induction of flowering by DNA demethylation in Perilla frutescens and Silene armeria: Heritability of 5-azacytidine-induced effects and alteration of the DNA methylation state by photoperiodic conditions. Plant Science, 178, 321-326

Is Epigenetic Status of Cancer Cells Influence Telomere Length?

Is Epigenetic Status of Cancer Cells Influence Telomere Length?


Telomeres are specialised chromatin structures essential for chromosome end protection and chromosomal stability are located at the end of the eukaryotic chromosomes and contain DNA sequences that are repeated many times. In normal (non-cancerous) human somatic cells telomere contain about 500 to 3000 TTAGGG repeats and are gradually shorten with age whereas in cancer cells do not shorten with age. It has also been found that cells with longer telomere length survive longer and go through more cell divisions than cells with shorter telomeres.

In recent studies it is found that in more than 90% of all cancer types in human tumours there is an increase in telomerase activity, an enzyme involved in regulation of telomere length. This shows that a certain minimum length of telomeres is necessary to maintain in order to sustain tumour growth. Thus one of the ways to combat cancer is to control telomere length by inhibiting telomerase activity and also other possible mechanisms that regulate telomere length in cancer cells.

REFERENCE:

Vera, E, Canela, A, Fraga, MF, Esteller, M & Blasco MA 2008, ‘Epigenetic regulation of telomeres in human cancer’, Oncogene, vol. 27, no. 54, pp. 6817-6833.

Jameris Dkhar
42256049

Disturbs of brain development can lead to adult to adult behavioral deficits, let’s check it out!

The neuronal network formation during development influences adult brain function, so that any disturbance at this stage is suggested to trigger the pathology of adult mental disorders. On the basis of this fact, the consequences of knocking down genetic susceptibility factors, for disorders such as schizophrenia, have been elucidated by the present study.

By using an innovating technique – In Utero Gene Transfer – this research group modulated the expression of target genes in the prefrontal cortex, and then they follow the development of the brain and how these changes may influence high brain functions as cognition and information processing.

In order to follow these changes from early brain development to postnatal brain maturation mice with selective knockdown were generated in this study. The importance of the use of animal models is also shown in this research, as these models can help us to be clear in aspects such as the consequences in high brain functions in adults of the disturbances in early development.

REFERENCE: M. Niwa, et al. Knockdown of DISC1 by In Utero Gene Transfer Disturbs Postnatal Dopaminergic Maturation in the Frontal Cortex and Leads to Adult Behavioral Deficits. Neuron, Volume 65, Issue 4, Pages 480-489

Maria Cristina Rondon

42142012