In:
eLife, eLife Sciences Publications, Ltd, Vol. 2 ( 2013-12-31)
Abstract:
Understanding how genes are activated and silenced is one of the central challenges in modern biology. These processes underpin the development of a fertilized egg into a complex organism, and they can also lead to life-threatening diseases when they go wrong. There are two copies of each gene in a human cell, a maternal copy and a paternal copy, and it is thought that both copies are usually regulated together. However, there are exceptions to this rule: for certain genes only the maternal copy is expressed as a protein in some cells, whereas the paternal copy is expressed in other cells. This form of gene regulation, which is called monoallelic expression, can result in neighboring cells heading down very different paths. In extreme cases, depending on the differences between the two copies of the gene, cells that express one copy may function normally, while cells where the other copy is activated will start forming tumors. However, despite these potentially grave consequences, and early results which suggested that monoallelic expression affected a large number of human and mouse genes, it has proved to be a major technical challenge to identify these genes in most cell types. Now, Nag, Savova et al. have discovered a molecular signature that can be used to detect monoallelic expression. The signature was found in chromatin, the densely packed structure formed by DNA and proteins inside the cell nucleus. Nag, Savova et al. discovered that the genes that are subject to monoallelic expression are bound with proteins that are modified in two contrasting ways. One modification, which is usually a sign of gene silencing, is prevalent on the inactive copy of the gene, and the other, which often marks active genes, is chiefly present on the active copy. Nag, Savova et al. report that these modifications are found in different sets of genes in different cell types, indicating distinct genome-wide patterns of monoallelic expression. The chromatin signature approach lets them estimate the fraction of human genes that are subject to monoallelic expression. This number is surprisingly high: about 20% of commonly expressed genes and more than one-third of tissue-specific genes. In a particularly intriguing finding, almost all bivalent genes—a subset of genes that are involved in determining the fate of cell during development—are estimated to become monoallelic when they are activated. In addition to these unexpected findings, the chromatin signature approach opens the door to exploring monoallelic expression as a form of gene regulation in all types of cells and, ultimately, to understanding how it is involved in both normal development and in disease.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.01256.001
DOI:
10.7554/eLife.01256.002
DOI:
10.7554/eLife.01256.003
DOI:
10.7554/eLife.01256.004
DOI:
10.7554/eLife.01256.005
DOI:
10.7554/eLife.01256.006
DOI:
10.7554/eLife.01256.007
DOI:
10.7554/eLife.01256.008
DOI:
10.7554/eLife.01256.009
DOI:
10.7554/eLife.01256.010
DOI:
10.7554/eLife.01256.011
DOI:
10.7554/eLife.01256.012
DOI:
10.7554/eLife.01256.013
DOI:
10.7554/eLife.01256.014
DOI:
10.7554/eLife.01256.015
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2013
detail.hit.zdb_id:
2687154-3
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