Epigenetics
"This volume is an excellent collection of advanced review papers on different aspects of the emerging research field of epigenetics ... the specific attraction of this volume is its comprehensive coverage of a complex and newly evolving research domain in light of different established disciplines that are currently investigating hitherto-unknown novel aspects of epigenetics in the context of their specific fields ... will serve as an essential primer for anyone interested in the dynamic evolution of epigenetics research ... One of the greatest strengths of this edited work is the variety of researchers contributing to the dynamics of the work's comprehensive nature ... an excellent resource on general aspects of epigenetics. It will quite effectively cater to the needs of molecular biologists, molecular geneticists, cell and molecular biologists, animal, plant, and crop geneticists, synthetic biologists, biotechnologists, and researchers involved with the fields of stem cell and molecular aspects of cancer research." from S.K. Basu and A. Goyal, Agriculture and Agri-Food Canada writing in Crop Science (2009) 49: 1937-1938 read more ...

Labels: Book on epigenetics, book review, books, epigenetics

Epigenetics is the study of meiotically and mitotically heritable changes in gene expression which are not coded for in the DNA. Exactly how these epigenetic modifications are directed to the particular gene and the local chromatin has remained enigmatic. Three distinct mechanisms appear to be intricately related and implicated in initiating and/or sustaining epigenetic modifications; DNA methylation, RNA-associated silencing, and histone modifications.

In human cells RNA can specifically direct epigenetic modifications to targeted loci (the promoter regions) and modulate silencing. This regulatory effect is through RNA-associated silencing, can be transcriptional in nature, and is operable through an RNA interference based mechanism (RNAi) that is specifically mediated by the antisense strand of small-interfering RNAs (siRNAs). These recent observations represent a paradigm shift in which a hidden layer of complexity is involved in gene regualtion and is operative via the action RNA essentially epigenetically regulating DNA.

from Kevin V. Morris (2008). RNA Mediated Transcriptional Gene Silencing. In: Morris, K.V. (Ed.) RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press, Norfolk, UK.

Further reading:

1. Epigenetics
2. RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity
3. Molecular Biology Books

Labels: epigenetics, expression, gene regulation, regulation, RNA, RNAi, siRNA

Heterochromatin is a prevalent chromatin state among eukaryotes that has critical functions in chromosome segregation, control of genomic stability and epigenetic regulation of gene expression. In the fission yeast Schizosaccharomyces pombe, two RNAi complexes, the RNAi-induced transcriptional gene silencing (RITS) complex and the RNA-directed RNA polymerase complex (RDRC), are part of a RNAi machinery involved in the initiation, propagation and maintenance of heterochromatin assembly. These two complexes localize in a siRNA-dependent manner on chromosomes, at the site of heterochromatin assembly. RNA polymerase II (RNApII) has a central role in RNAi-dependent heterochromatin assembly. RNApII synthesizes a nascent transcript that serves as an RNA platform to recruit RITS, RDRC and possibly other complexes required for heterochromatin assembly. Both RNAi and an exosome-dependent RNA degradation process contribute to heterochromatic gene silencing. Recently reported findings challenge the widely accepted view that heterochromatic gene silencing is caused strictly by chromatin compaction. As RNAi-dependent chromatin modifications have been observed throughout the eukaryotic kingdom the mechanisms described here may be utilized in a large range of eukaryotes.

from Vavasseur et al in RNA and the Regulation of Gene Expression

Further reading: Epigenetics

Labels: epigenetics, regulation, RNA, RNAi, siRNA, yeast

Regulation of gene expression is a complex, multi-layered process that is crucial to correctly drive and maintain cell identity during development and adult life. RNA interference (RNAi) and the Polycomb system are two well-conserved gene silencing pathways. RNAi participates in post transcriptional as well as transcriptional gene silencing of natural genes as well as transposons and viruses. Polycomb group (PcG) proteins are well-known for their role in silencing HOX genes through modulation of chromatin structure. Both mechanisms are involved in specific epigenetic processes like cosuppression in Drosophila melanogaster and the formation of C. elegans mes and SOP-2 complexes. There are molecular links between RNAi components and Polycomb-mediated silencing in human cells and in Drosophila. RNA polymerase II and Argonaute 1 interact to bring about chromatin modifications on endogenous Polycomb target gene promoters in human cells, while Drosophila RNAi components modulate the nuclear organization of PcG target DNA elements, thereby affecting the strength of PcG-mediated silencing. Several microRNAs and non coding RNAs have been found in human and fly HOX gene loci. They may regulate HOX gene expression both post-trascriptionally and co-transcriptionally.

from Portoso and Cavalli in RNA and the Regulation of Gene Expression (Chapter 3)

Labels: Drosophila, epigenetics, polycomb, regulation, RNA, RNAi

Epigenetics is the study of meiotically and mitotically heritable changes in gene expression which are not coded for in the DNA. Three distinct mechanisms appear to be intricately related and implicated in initiating and/or sustaining epigenetic modifications; DNA methylation, RNA-associated silencing, and histone modifications. While chromatin remodeling and DNA methylation have been studied for several years now far less is know about how these epigenetic marks are directed to each particular gene. Recently, however the role of RNA in epigenetic gene regulation has begun to become apparent.

from Kevin V. Morris in "Chapter 2 Epigenetic Regulation of Gene Expression" from RNA and the Regulation of Gene Expression

Further reading:

1. RNA and the Regulation of Gene Expression
2. Epigenetics

Labels: epigenetics, expression, regulation, RNA

The field of epigenetics has gained great momentum in recent years and is now a rapidly advancing field of biological and medical research. Epigenetic changes play a key role in normal development as well as in disease.

The term epigenetics was coined by the developmental biologist Conrad Waddington to describe "the interactions of genes with their environment which bring the phenotype into being". This was recognition of the fact that it is not only the DNA sequence that determines the phenotype. All cells of a multicellular organism carry the same genetic material coded in their DNA sequence, but cells obviously display a broad morphological and functional diversity. Epigenetics is the branch of biology that studies the additional layers of information, in addition to the bare genomic sequence, that dramatically extend the information potential of the genetic code. Epigenetics, therefore, is the study of heritable changes in the cellular state that are not caused by changes in the nucleotide sequence of the DNA. Epigenomics is a new science unifying epigenetics and genomics and studying epigenetic modifications at high-throughput and/or on a whole genome level.

DNA methylation is the only genetically programmed DNA modification in mammals and probably the best studied epigenetic modification. Cytosine methylation at CpG positions of the DNA sequence is one of the hallmarks of epigenetic gene silencing. During evolution, CpG rich regions, so-called CpG islands, have been established as prominent features of promoter regions of genes. Whereas most regions of the genome are constantly methylated these elements are mainly kept free of methylation thereby facilitating the establishment of an open chromatin structure and of initiation of transcription. Besides its role in the regulation of genes, DNA methylation silences repetitive elements and appears to be important for the stability of the mammalian genome.

DNA-associated histone proteins play an important role in gene regulation within the mammalian genome. Various covalent chemical modifications of the histones are possible and can directly affect various DNA-templated processes such as transcription.

Polycomb and Trithorax group proteins are important epigenetic regulators of homeotic genes. They play a broad role in cell differentiation, which is exerted through the direct control of hundreds of transcription factors as well as important signaling proteins and morphogens. Polycomb silencing is a dynamic process intimately dependent on histone modifications and balanced by antagonistic action of Trithorax proteins.

In eukaryotic cells, the majority of transcribed RNAs are non-coding RNAs (ncRNAs). It is evident that ncRNAs are functionally involved in many biological processes, such as proliferation, differentiation and development. NcRNAs function as regulators of gene expression on various levels, including chromatin modification, transcription, RNA modification, RNA splicing, RNA stability and translation.

Genetic and epigenetic mechanisms contribute to the development of human tumors. Research into the differences between normal and cancer epigenomes, and the knowledge gained from single gene and large-scale epigenome analyses provide important information relevant to for gene discovery, therapeutic applications, and building a mechanism-based model of human tumorigenesis.

DNA methylation, chromatin structure, Polycomb proteins and non-coding RNAs are areas of current research and part of the fascinating and fast moving field of epigenetics.

Further reading: Epigenetics

Labels: epigenetics