A phenomenon called "chromatin looping" occurs when the structural material that encases DNA (chromatin) forms a loop, bringing distant genes closer to promoters that reside far away on the genetic strand. Chromatin looping was initially observed in 2002 but recent work from HSCI Principal Faculty Daniel Tenen is the first to identify a specific protein whose job is to facilitate this process. Scientists have long known that the protein RUNX1 helps stem cells become hematopoietic stem cells (HSCs), the precursors to blood cells, but until now the details of this mechanism were still unclear. Tenen and his team chose to probe RUNX1 for its interactions with DNA in mice. They found that the protein binds to an area of the genome far away from a gene called CD34 whose expression gives HSCs their distinctive character. When RUNX1 is not allowed to bind to this promoter area, CD34 is not expressed and stem cells do not become HSCs. They also found evidence that the other proteins in the RUNX family may facilitate other chromatin loops, suggesting that RUNX proteins may play a more general role in mediating these kinds of interactions. With this information, scientists can probe the RUNX1 protein and others in the RUNX class for genetic mutations that lead to various blood diseases.

Levantini, E.; Lee, S.; Radomska, H.; Hetherington, C.; Alberich-Jorda, M.; Amabile, G.; Zhang, P.; Gonzalez, D.; Zhang, J.; Basseres, D.; Wilson, N.; Koschmieder, S.; Ebralidze, A.; Bonifer, C.; Okuno, Y.; Gottgens, B.; Tenen, D. (2011) RUNX1 regulates the CD34 gene in haematopietic stem cells by mediating interactions with a distal regulatory element. EMBO Journal Epub 2011 August 26.