Chromatin regulates the transfer of genetic information, which is essential for the correct development and function of a human being. Originally, chromatin was identified in 1882 as not much more than the coloured substance of the cell nucleus and it was named according to the Greek word ‘chroma’, meaning colour. Later chromatin was characterised as proteins attached to DNA, and the DNA was identified as the carrier of the genetic information.
DNA was believed to contain ‘all’ the information, and chromatin was thought to be ‘just’ a way of packaging about 2 meters of DNA into a small nucleus of only a few μm in diameter. In the 1980s this view drastically changed, and we now know that chromatin proteins are instrumental in regulating the transfer of genetic information.
Genetic information is transferred at three different stages: replication, transcription and translation. First, in DNA replication the genetic information is duplicated and transmitted from one cell to its daughter cells. Second, in transcription the genetic information (genes) is copied from DNA into mRNA. Third, in translation this mRNA is used as a template to generate proteins which have specific biological functions. This central dogma of molecular biology provides the foundation – but does not explain the entire complexity – of life.
Knowing only the information in the DNA is not enough to understand a complex organism, such as a human being. To do so, we need to understand what regulates the transfer of genetic information into mRNA and proteins. Then we can answer questions like: How come the cells in your liver are so different from those in your skin or muscles, while they have the same DNA? How can some genes be switched off while others are switched on? Why is this different between different cell types?
There is a number of chromatin forms. And so in the early 2000s we knew that genes in ‘silent’ chromatin are generally switched off, while genes in ‘active’ chromatin are switched on, but we did not know this for all the genes in the genome and we did not know how many different forms of chromatin existed. My colleagues in Amsterdam and I therefore set out to analyse the chromatin composition of the entire genome, using the fruit fly as a model organism. We identified 5 distinct chromatin types, defined by unique combinations of proteins. In line with the word ‘chroma’ we named these five types by the colours: YELLOW, RED, GREEN, BLUE and BLACK. YELLOW and RED are active, GREEN and BLUE are less active, while BLACK is totally inactive.
All active genes were always thought to have one chromatin type, but we found them to be separated in two very distinct types: RED and YELLOW. Genes in YELLOW chromatin are switched on in almost all cells because every cell needs them, whereas genes in RED are specifically switched on in different cell types, because they have more specific functions. GREEN and BLUE chromatin correspond to two well-known chromatin types and for a long time these chromatin types were called inactive chromatin. We found only a small part of the inactive genes in GREEN or BLUE chromatin, and these genes were not even completely switched off. The majority of the inactive genes in the fruit fly cells were actually having the novel BLACK chromatin type.
Discovering these colourful chromatin types showed for the first time how the genetic information is organised and regulated. Since then a similar chromatin organisation was found in the human genome, providing us with new understanding about how genetic information in the DNA gives rise to a complex organism like a human being.
About the author:
Joke van Bemmel completed her PhD on chromatin composition in the lab of Bas van Steensel at the Dutch Cancer Institute in Amsterdam, the Netherlands. She is currently working as a postdoc in the lab of Edith Heard at the Institute Curie in Paris, France, where she studies the three-dimensional chromatin conformation of the X-chromosome in mouse embryonic stem cells. She is passionate about communicating science to non-scientists, she co-organized an Art&Science exhibition in Paris and in her free time she loves to climb rocks at different places around the world.