Making and breaking heterochromatin

To fit the two-meter long DNA molecule into a cell nucleus that is only a few thousandths of a millimetre in size, long sections of the DNA must be strongly compacted.

Epigenetic marks maintain these sections, known as heterochromatin. Scientists of the Max Planck Institute of Immunobiology and Epigenetics in Freiburg have now discovered two further mechanisms necessary for the formation of heterochromatin.

The research group, led by Thomas Jenuwein, describes two novel enzymes, Prdm3 and Prdm16, which attach a methyl group to a particular packaging protein of the DNA. These epigenetic marks assure that heterochromatin, and with it the structure of the cell nucleus, remain intact.

Moreover, in an additional study they have determined that transcription factors bind within heterochromatin and repress the output of non-coding RNA. In contrast to less densely compacted regions known as euchromatin, in which the transcription factors accumulate at specific sites, the binding sites of transcription factors in heterochromatin are much more randomly distributed.

Chromatin consists of the DNA molecule and numerous proteins, including histones, which act as packaging proteins. In contrast to the easily accessible euchromatin, which contains the majority of genes, the densely compacted heterochromatin is mostly made of up of repetitive sequences that are able to form non-coding RNA-molecules. Heterochromatic sections are found at centromeres and at chromosome ends, the telomeres.

Chemical modifications of histones can alter the degree to which chromatin is compacted. For example, methyltransferases add methyl groups to proteins at various positions. These epigenetic alterations regulate the formation and maintenance of heterochromatin.