Two major publications from the FANTOM5 project provide details of how genes are regulated to build the body. The work contributes to our growing knowledge of the genome functions in the body.
Published in the open access journal, BMC Genomics, the two articles suggest the importance of chromatin states – the way the DNA is structured within the nucleus - for defining how and when proteins are produced in human cells, and suggest that DNA methylation may not be as universal a method as previously thought for repressing particular genes.
The FANTOM5 (Functional annotation of the mammalian genome) project intends to answer the question of how different cell types are encoded in our genomes. These articles, published in coordination with others in Nature, Blood, and 7 other journals illustrate important advances in our knowledge about this area.
In a paper by Rye et al, scientists used data from the FANTOM5 project and ENCODE project to investigate chromatin state, and how this relates to what genes are activated in each cell. Their research confirms a link, and also suggests that chromatin states may play an important role where particular genes have been repressed by other methods as a cell doesn’t need a protein all the time, but might need to activate it quickly. The researchers saw that immune related genes that had been repressed showed ‘active’ chromatin states, suggests that this marker might prime those genes for immediate activation in reaction to particular environmental stimuli.
The second article, by Medvedeva et al., focused on DNA methylation. This is widely known to be involved in the repression of genes, so that the protein they code for isn’t produced. Previously, scientists were unsure whether the DNA methylation was a symptom or a cause of gene repression. This analysis of the instances where DNA methylation was associated with gene repression suggests that direct and selective blocking of transcription factor binding sites only occurs in particular cases. The authors suggest that this might mean it’s unlikely to be a general method of gene repression.
These findings will help scientists to build a picture of how the genome functions in the body.
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Notes to Editor
1. Effects of cytosine methylation on transcription factor binding sites
Yulia A Medvedeva, Abdullah M Khamis, Ivan V Kulakovskiy, Wail Ba-Alawi, Md Shariful Bhuyan, Hideya Kawaji, Timo Lassmann, Matthias Harbers, Alistair RR Forrest and Vladimir B Bajic
BMC Genomics (Section: Human and rodent genomics) 15: 119 doi:10.1186/1471-2164-15-119
Available at: http://0-www.biomedcentral.com.brum.beds.ac.uk/1471-2164/15/119
Chromatin states reveal functional associations for globally defined transcription start sites in four human cell lines
Morten Rye, Geir K Sandve, Carsten O Daub, Hideya Kawaji, Piero Carninci, Alistair RR Forrest and Finn Drabløs
BMC Genomics (Section: Human and rodent genomics) 15: 120 doi:10.1186/1471-2164-15-120
Available at: http://0-www.biomedcentral.com.brum.beds.ac.uk/1471-2164/15/120
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These papers are published in coordination with papers in Nature and Blood.
The papers in Nature are:
A promoter-level mammalian expression atlas
An atlas of active enhancers across human cell types and tissues
More information is available from the Nature press office at firstname.lastname@example.org
The papers in Blood are:
Redefinition of the human mast cell transcriptome by deep-CAGE sequencing, Motakis et al.
High-throughput transcription profiling identifies putative epigenetic regulators of hematopoiesis, Prasad et al.
Transcription and enhancer profiling in human monocyte subsets, Schmidl et al.
The enhancer and promoter landscape of human regulatory and conventional T cell subpopulations, Schmidl et al.
Analysis of the DNA methylome and transcriptome in granulopoiesis reveal timed changes and dynamic enhancer methylation, Rönnerblad et al.
More information is available from the Blood press office from Amanda Szabo email@example.com
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