The study, published in Cell Reports, also shows that the DNA elements regulating Wnt4 differ substantially between mice and humans. The work provides fundamental insight into how the non-coding genome contributes to health and disease.
More than protein-coding DNA
Every cell in the human body contains around two metres of DNA. Yet only a small proportion of that DNA contains instructions for making proteins. Much of the remaining, non-coding DNA helps regulate which genes are switched on in different cell types and at different stages of development. Researchers in the Developmental, Stem Cell and Cancer Biology group at SILS investigated this regulatory system for Wnt4. This gene is particularly important in the mammary gland, which undergoes major changes during puberty, pregnancy and lactation.
During early pregnancy, for example, the hormone progesterone stimulates the development of milk-producing structures called alveoli. However, progesterone does not act directly on every cell in the tissue. Instead, specialised hormone-responsive cells receive the signal and activate genes including Wnt4. The proteins encoded by these genes then pass local growth signals to neighbouring cells. Led by Prof. dr. Renée van Amerongen, the researchers examined the first stage of this signalling process: how cells recognise that Wnt4 should be switched on, and which parts of the genome are involved.