A protein that masterminds the way DNA is wrapped within chromosomes has a major role in the healthy functioning of blood stem cells, which produce all blood cells in the body, according to a new study from researchers at Weill Cornell Medicine.
The protein, known as histone H3.3, organizes the spool-like structures around which DNA is wrapped in plants, animals and most other organisms. Histones enable DNA to be tightly compacted, and serve as platforms for small chemical modifications—known as epigenetic modifications—that can loosen or tighten the wrapped DNA to control local gene activity.
The study, which appeared Dec. 27 in Nature Cell Biology, examined H3.3’s role in blood stem cells, also known as hematopoietic stem cells (HSCs), that are a major focus of efforts to develop stem-cell-based medicine. Normally most HSCs stay in a stem-like, uncommitted state where they can survive long-term, slowly self-renewing, while some HSCs mature or “differentiate” to produce all the different lineage-specific blood cell types. The study found that H3.3 is crucial for both processes; deleting the protein from HSCs led to reduced HSC survival, an imbalance in the types of blood cell produced by the HSCs and other abnormalities.
