Science Functional Genomics Resources

CoverFor decades, our view of heredity has been written in the language of DNA -- and genetic mutations and recombinations have driven most descriptions of how phenotypic traits are handed down from one generation to another. Yet, as is amply demonstrated in Science's special issue of 10 August 2001, recent discoveries in the field of epigenetics -- the study of heritable changes in gene function that occur without a change in the DNA sequence -- have blurred that neat picture, and are changing the way researchers think about heredity. Epigenetic mechanisms such as DNA methylation, histone acetylation, and RNA interference, and their effects in gene activation and inactivation, are increasingly understood to be more than "bit players" in phenotype transmission and development. And, with the prospect of human cloning now being actively discussed in some quarters, understanding the twists and turns of epigenetic inheritance has become especially important.

To provide an extra dimension to coverage in the 10 August 2001 special issue, we're launching a new epigenetics section here on the Science Functional Genomics Web site. On this page, you'll find a collection of links to interesting Web resources on chromatin, methylation, imprinting, and a variety of other topics with an epigenetics bend. Also, we've gathered together a selection some groundbreaking research papers, Reviews, and Perspectives published in Science over the past five years, in a special new epigenetics section of our Functional Genomics Research Archive.

General Information on Epigenetics

Commonly defined as the study of heritable changes in gene function that occur without a change in the DNA sequence, epigenetics is reshaping the way scientists look at traditional genetics. Following is a selection of online general information and review articles on this emerging field.

Epigenetics: Regulation Through Repression
Review article published in Science that explores the mechansims of epigenetic control (DNA- and RNA-based) and the role those mechanisms play in development, disease, and human evolution.
Toward an Epigenetic Biology and Medicine
Interesting article that argues that our current understanding of genetics is oversimplified, and maintains that, because of epigenetic characteristics, genomes are more complex then the sum of their genes.
The Paradigm of Differential Gene Expression
Part of an online accompaniment to Gilbert's Developmental Biology, this section explores a range of different mechanisms for controlling gene expression.

Histones, Chromatin, and Chromosome Structure

Fitting a strand of DNA roughly six feet long into the nucleus of a cell, histones are the real organizers of the human body. Access to genes wrapped around these proteins to form chromatin and chromosomes plays an integral role in regulation of gene expression and cellular mechanisms. Here are some Web resources exploring the realm of chromosome formation and histone modification.

Chromatin Structure and Function Page
Well-known and useful site for those studying chromatin structure, maintained by J. R. Bone. Especially handy are a Listserv of hot papers on chromatin-related topics, links to resources for major chromatin proteins, and a database of chromatin protocols.
Waterborg's Chromatin Home Page
Visually active site that contains well-illustrated slide shows on nucleosome formation, histone acetylation, and histone variants. A good way to visualize chromosome formation.
A Few Words about DNA and Chromatin
Review of the structure of DNA and the orginization and assembly of chromatin, by Robert Stewart of the Biological Effects of Radiation and Chemicals group at the Pacific Northwest National Laboratory.
A Microscopists' View of Chromosome Organization
Superb page -- amply illustrated with crisp electron micrographs -- that aims "to show how cytologists and cytochemists contribute to our understanding of the organization of nuclear chromatin." Part of a larger collection of cell biology Web pages assembled by Gwen Childs, University of Arkansas.
Eukaryotic Chromosome Structure
Overview of the chromosome, with links to information and animations of DNA replication.
Chromatin Network
Euchromatin Network
Information on the history of chromatin discovery, with a number of references to other papers.
A "link page written for chromosome scientists," Chromosome@net provides readers with lists of upcoming conferences, protocols, directories, laboratories, and more.
The Making of the Nucleosome
Cartoonlike visual tour of the formation of the nucleosome, complete with individual chromatin drawings.

Methylation, Imprinting, Gene Silencing, and RNA Interference

Following are Web sites dedicated to the processes by which genes are controlled epigenetically.

DNA Methylation Society
Home page of a scientific association "open to all those interested in any aspects of biological methylation." A brief description, "What is DNA methylation?", provides an introduction. Site also includes information on upcoming meetings on methylation, molecular structure files of methylated DNA, and (for society members) abstracts of current research.
DNA Methylation
Visual aid that uses molecular models to show three different types of DNA methylation.
DNA Methylation and Genomic Imprinting
Short, well-crafted student essay discussing DNA methylation's role in mammalian genomic imprinting. Part of the Virtual Embryo site at the University of Calgary.
A good resource for information on genomic imprinting, this site contains recent imprinting news, upcoming conferences, research papers, and links to laboratories.
BioTech Info -- Gene Silencing
Information, papers, and abstracts concerning gene silencing, from the Ag BioTech InfoNet Web site.
RNA Interference and Gene Silencing
A special feature from biotech company Ambion, this article reviews the discovery and potential applications of gene silencing due to RNA interference.

Epigenetics and Disease

In the finely tuned world of the nucleus, even the slightest misstep can produce devistating results. Here, we've gathered a selection of sites on diseases caused by some mistakes in epigenetic control.

National Cancer Institute
Clearinghouse for cancer research and information, including study of cancer epigenetics. Features the superb public-outreach gateway site CancerNet.
International Rett Syndrome Homepage
Contains a primer on Rett Syndrome (a neurological disorder thought to be related to X-chromosome inactivation), research news, support links for sufferers, and Rettnet, a moderated online forum for all persons interested in Rett Syndrome.
Rett Syndrome Research Foundation
Information about funding opportunities and current research concerning Rett Syndrome.
How Does Methylation Control Synthesis of Proteins?
Part of the National Fragile X Foundation Web site, this page offers a plain-language discussion of "good" and "bad" methylation -- and explains how the latter plays a key role in fragile X syndrome.
FRAXA Research Foundation
Website from the Fragile X Association Research Foundation containing news and information on Fragile X syndrome and current research.
Fragile X Syndrome - What Is It?
Fantastic multimedia factsheet on fragile X syndrome, its symptoms, its causes, its incidence, and other information, aimed at the general public. Part of the Cold Spring Harbor Laboratories Your Genes, Your Health site.

Selected Databases

MethDB (DNA Methylation Database)
Allows users to search methylation patterns and profiles from a list of sequenced genes. Described in an article in the 2001 database issue of Nucleic Acid Research.
Histone Sequence Database
Database of histones and histone fold-containing proteins. Site also includes human histone gene complements and post-transcriptional modifications.
Atlas of DNA Structures
Online atlas of A,B, and Z confirmations of DNA including mismatches, modifiers, and special features.
Mouse Imprinting Map
Gene imprinting in mice; contains data, chromosomal maps, and references relating to imprinted genes and chromosome regions with imprinting phenotypes.
Histone Acetyltransferase Page
Information on proteins that acetylate core histones, with visual aids and links to PubMed references.

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