from Genetic Engineering News Market and Technology Analysis The focus of this GEN Market & Tech Analysis report is to More »
Large-scale mapping of transcriptomes has revealed significant levels of transcriptional activity within both unannotated and annotated regions of the genome. More »
The H19 gene controls the expression of several genes within the Imprinted Gene Network (IGN), involved in growth control of More »
Chromosome conformation capture-on-chip analysis of long-range cis-interactions of the SOX9 promoter
Evolutionarily conserved transcription factor SOX9 is essential for the differentiation of chondrocytes and the development of testes. Heterozygous point mutations More »
from Genetic Engineering News
Market and Technology Analysis
We present here long-range epigenetic silencing (LRES) as a means for downregulation of stretches of the genome as well as long-range epigenetic activation (LREA). These two opposing effects appear to be mediated by an interplay between DNA methylation and chromatin modification. We’ve focused this analysis on an interrogation of prostate cancer.
from The Economist
A newly recognised class of genes really does matter
GENETICS often progresses by breaking things. Early experiments used naturally broken genes—mutations—to work out the basic rules. Then geneticists found out how to induce mutations with radiation and chemicals. That gave them more material to work with, but the mutations still appeared at random. Then the “knockout mouse” was invented, in which mice have specified genes rendered inoperable, thus revealing their functions. Now, as they write in eLife, John Rinn of Harvard University and his colleagues have used the idea of knockouts to prove that certain bits of DNA once regarded as junk are proper genes after all.
The DNA in question is propagated by being copied—as are all genes—into a similar molecule called RNA. In the case of conventional genes this RNA is then “translated”, in a subcellular machine called a ribosome, into a protein. Dr Rinn’s RNA—a type known as long intergenic non-coding RNA, or lincRNA—is not so translated. Geneticists used to assume that this meant it was useless. Now they know different: it actually goes off to do jobs uniquely suited to the chemistry of RNA itself. How important those jobs are, though, has been much debated. Dr Rinn has just demonstrated, by knocking out 18 lincRNAs, one at a time, and observing what happened to the mice in question, that they can be very important indeed.
Large-scale mapping of transcriptomes has revealed significant levels of transcriptional activity within both unannotated and annotated regions of the genome. Interestingly, many of the novel transcripts demonstrate tissue-specific expression and some level of sequence conservation across species, but most have low protein-coding potential. Here, the authors describe progress in identifying and characterizing long noncoding RNAs (lncRNAs) and review how these transcripts interact with other biological molecules to regulate diverse cellular processes. They also preview emerging techniques that will help advance the discovery and characterization of novel transcripts. Finally, they discuss the role of lncRNAs in disease and therapeutics.
- Yang L, Froberg JE, Lee JT. (2013) Long noncoding RNAs: fresh perspectives into the RNA world. Trends Biochem Sci [Epub ahead of print]. [abstract]
The H19 gene controls the expression of several genes within the Imprinted Gene Network (IGN), involved in growth control of the embryo. However, the underlying mechanisms of this control remain elusive. Here, researchers from the CNRS, France identified the methyl-CpG–binding domain protein 1 MBD1 as a physical and functional partner of the H19 long noncoding RNA (lncRNA). The H19 lncRNA–MBD1 complex is required for the control of five genes of the IGN. For three of these genes—Igf2 (insulin-like growth factor 2), Slc38a4 (solute carrier family 38 member 4), and Peg1 (paternally expressed gene 1)—both MBD1 and H3K9me3 binding were detected on their differentially methylated regions. The H19 lncRNA–MBD1 complex, through its interaction with histone lysine methyltransferases, therefore acts by bringing repressive histone marks on the differentially methylated regions of these three direct targets of the H19 gene. This data suggest that, besides the differential DNA methylation found on the differentially methylated regions of imprinted genes, an additional fine tuning of the expressed allele is achieved by a modulation of the H3K9me3 marks, mediated by the association of the H19 lncRNA with chromatin-modifying complexes, such as MBD1. This results in a precise control of the level of expression of growth factors in the embryo.
- Monnier P, Martinet C, Pontis J, Stancheva I, Ait-Si-Ali S, Dandolo L. (2013) H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1. Proc Natl Acad Sci U S A [Epub ahead of print]. [abstract]
from Biology Computes
Ying Sha, Sanjeev Sariya, Ali M Pirani, Adrian Lawsin
•Chromatin remodeling: Hetrochromatin to Euchromatin – The well-characterised lncRNAs ANRIL, XIST, HOTAIR and KCNQ1OT1 are able to recruit epigenetic modifiers to specific loci to reprogram the chromatin state.