Tumor suppressor p16INK4A regulatespolycomb-mediated DNA hypermethylation in human mammary epithelial cells

Several markers are used for the identification of breast cancer progression in women, these include an upregulation of the ER α, ER β, PR etc. The pattern of gene expression leading to this is a very hot topic of scientific research. In this article, the authors propose a model where loss of p16^INK4A function in the mammalian epithelial cells stimulated the upregulation of polycomb group (PcG) of proteins to form repressor complexes which bound and transcriptionally silenced loci involved in cell-fate processes. A candidate is the HOX9A locus, which transcribes genes necessary for lactational differentiation and is absent in breast cancer cells. The eventual result is the de novo DNA hypermethylation. The data from this study suggest that the epigenetic changes initiated by loss of p16^INK4A activity are among the earliest events in breast tumor progression.

Kim Nguyen

Epigenetic Reactivation of Tumor Suppressor Genes by a Novel Small-Molecule Inhibitor of Human DNA Methyltransferases

An important way for gene expression regulation in both normal and malignant cells is DNA methylation (a common method of gene silencing). Furthermore, by development of DNA methyltransferase inhibitors the possibility to reactivate epigenetically silenced genes has generated. (Cancer Res 2005; 65(14): 6305-11)

From biochemistry point of view it is very important to find enzyme inhibitors for particular pathway it will help to study or regulate this pathway. This article provides a novel small molecule (RG108) which acts as an inhibitor for DNA methyltransferases in vitro and results in demthaylation and reactivation of tumor suppressor gene. The results of this study maybe very promising for cancers therapy.

I am also interested in this topic because it is amazing how the environment and drugs can have grate influence on some of our genes.

Submitted by: Mazin ZAMZAMI
School of Molecular and Microbial Sciences
University of Queensland
06 September 2006

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Histones and their modifications play a critical role in transcriptional silencing in yeast

The heritable features of an organism are determined not only by the contents of gene and also heavily depended on the way they expressed.
The researchers from University of California, USA have demonstrated evidences to show the important role of histones and their mutations in regulation of gene expressing. The researchers experiment indicated that the modifications of both the core area of nucleosomes and amino termini of histone H3 and H4 have strong impact to gene silencing. These mutations could enhance gene silencing at telomeres and increase the proporation of cells in which telomeres and mating-type loci are in the silent state.
This result may have an impact on research in the area of epigenetic regulation of gene expressing and genetic cancer therapy.

Selected by: Brian Xing

Title of paper: Mutations in the Nucleosome Core Enhance Transcriptional Silencing†

Regulation of MHC class II expression in human T-cell malignancies

An epigenetic silencing mechanism has been implicated in leukaemia of T-cells of the immune system.

Major Histocompatability Complex (MHC) class II proteins are an important part of the defense mechanism of the immune response, and are often lacking in tumorous cells. These MHC class II proteins require a transactivator, encoded by a gene called MHC2TA.

A promoter region upstream of this gene regulates production of the transactivator, and has been shown to be hypermethylated in leukaemic T-cells. Demethylating the DNA of these cells resulted in a re-expression of MHC class II defense antigens. This implies an important role for epigenetic factors in leukaemic T-cells.

Carl Morrow

Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells

Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells -- By Ropero et al. 13 (22): 2753 ( Human Molecular Genetics)

Hello friends.

This paper deals with Exostoses-1 gene (EXT1), mutations of which lead to Hereditary Multiple Exostoses(HME) syndrome, an autosomal dominant disease affecting the long bones of individuals from childhood to puberty and characterized by the formation of cartilage-capped tumors, known as osteochondromas or exostoses. Individuals with HME have a significantly higher risk than the general population of developing malignancies such as chondrosarcomas and osteosarcomas.

This gene EXT1, is a glycosyltranferase required for the biosynthesis of heparan sulfate glycosaminoglycans (HSGAGs), an important component of connective tissues . The study emphasizes the significance of Impaired Heparan Sulphate production in the biology of malignancy and epigenetic silencing of EXT1 gene as one of its key steps.

I am a medical graduate interested in human cancer research and that is the reason I chose this paper.

ChEeRs,

Suman Kumar

RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse

RNA RESPONSIBLE FOR HERITABLE CHANGES !!
BY: Rassoulzadegan, M. et al.
SOURCE: Nature 441, 469-474 (25 May 2006) .
NAME: PATEL NIRAV BHARATKUMAR.(41252361)

RNA can bring about heritable changes, this is something that is hard to believe is’nt it? But, based on the study carried out on mice it has been postulated that RNA can bring about heritable changes.
The study suggests that without the changes in the DNA structure there was a prominent change seen in the mice i.e. the white spots observed on the body. This is due to the fact that sperm and egg might trasmit the genetic information thorugh the RNA. The study involves paramutation : in this case, an allele interacts with its homologue and somehow causes in it a heritable epigenetic change.
Ok, wait for my review to learn and explore the facts!!!
Cheers,
NIRAV