SCIENCE

Exploring the transcriptome, illuminating chromatin

Using a variety of techniques, the researchers developed 700 new data sets of information on different aspects of the fly genome. The transcriptome group identified 17,000 genes, both coding and noncoding, of which 1,938 were new.

But DNA is surprisingly versatile – coding sequences, known as exons, can be spliced together in different ways to produce more than one form of a protein. The researchers found almost 53,000 new or modified exons and almost 23,000 new splicing junctions, with 14,000 alternative ways of transcribing the genetic information. Despite the scrutiny to which theDrosophila genome has been subjected, the researchers found new or altered exons or splice forms in almost three-quarters of Drosophila’s previously annotated genes.

Like all eukaryotes (organisms whose cell nuclei are enclosed within a membrane) Drosophila’s genome is divided among euchromatin, which contains many active genes, and heterochromatin, which – although it amounts to about a third of the genome – contains relatively few active genes. Thus the Drosophila chromatin group was surprised to discover that some regions of heterochromatin are almost as active in expression as euchromatin.

The mark of an active or silent chromatin region is the chemical state of its nucleosomes, specifically whether the histones, on which the DNA is wrapped, permit or prevent the RNA-constructing enzyme, RNA polymerase, to bind to the DNA for transcription. For example, acetylated histones generally promote transcription, while many methylated histones can repress transcription. The Drosophila chromatin group found that in some regions, what controlled gene expression could not be identified from the DNA sequence, yet these regions were marked by specific histone modifications and other epigenetic factors. They also found active regions of euchromatin that carried marks characteristic of heterochromatin, patterns that were a combination of both “active” and “silent” marks.

By identifying the combinatorial patterns of 18 different histone modifications, and analyzing their associations with gene expression and other functions, the group developed a model of chromatin states working in concert, and how these vary among different cell lines. Their model identified novel chromatin signatures associated with regulation of gene activity and other functions, as well as many previously unidentified genes and promoters.