The DNA in human cells is translated into a multitude of proteins required for a cell to function. When, where and how proteins are expressed is determined by regulatory DNA sequences and transcription factors. Transcription factors are proteins that bind to the regulatory DNA sequences. Each cell type can be distinguished based on its pattern of transcription factor binding. In certain cases, a cell can be directly converted from one type to another, simply by changing the expression of one or more transcription factors.

Maintaining cell identity
It is critical that the pattern of transcription factor binding be maintained during cell division. This ensures that daughter cells have the same function as their mother cell, so that for example muscle cells can contract or pancreatic cells can produce insulin. During each cell division, the transcription factors are removed from DNA and must find their way back to the right spot after the cell has divided.
"The problem is that there is so much DNA in a cell. It would be impossible for the transcription factors to find their way back within a reasonable time frame. But now we have found a possible mechanism for how this cellular memory works", explains Jussi Taipale, Professor at the Swedish Karolinska Institutet and head of the research team that made the discovery.

Ring marks the spot
The research group found that a large protein complex called ‘cohesin’ is positioned as a ring around the two DNA strands that are formed when a cell divides. The ring marks the places on the DNA where transcription factors were bound. This helps the transcription factors to find their original binding region on both DNA strands.
"More research is needed before we can be sure, but so far all experiments support our model", says Martin Enge, Assistant Professor at Karolinska Institutet.

Implications for patients
The discovery that regulatory DNA sequences bind to cohesin may also have consequences for patients with cancer or hereditary diseases because transcription factors play a pivotal role in these illnesses. Cohesin would function as an indicator of which DNA sequences might contain disease-causing mutations.
"Analysing DNA sequences that bind to cohesin would make it much easier to identify novel harmful mutations", Martin Enge concludes.

Further reading
Read the full press release about this work.
Read the publication in the scientific journal Cell.
Read the project SYSCOL, which is coordinated by Jussi Taipale.