Young Lab

A previously mysterious part of transcription factors, the activation domain, plays a key role in forming phase separated "droplets" that concentrate proteins required for transcription near genes

The Whitehead Institute community has lost Landon Clay, a true friend and an avid supporter of the Institute’s scientific mission and research. 

In a finding with enormous implications for cancer diagnostics and therapeutics, Whitehead Institute scientists have discovered that breaches in looping chromosomal structures known as “insulated neighborhoods” can activate oncogenes capable of fueling aggressive tumor growth. 

Whitehead Institute researchers have created a map of the DNA loops that comprise the three dimensional (3D) structure of the human genome and contribute to gene regulation in human embryonic stem cells. The location of genes and regulatory elements within this chromosomal framework will help scientists better navigate their genomic research, establishing relationships between mutations and disease development.

Scientists have long theorized that the way in which the roughly three meters of DNA in a human cell is packaged to fit within a nuclear space just six microns wide, affects gene expression. Now, Whitehead Institute researchers present the first evidence that DNA structure does indeed have such effects—in this case finding a link between chromosome structure and the expression and repression of key genes.

Having recently discovered a set of powerful gene regulators that control cell identity in a few mouse and human cell types, Whitehead Institute scientists are now showing that these regulators—which they named “super-enhancers”—act across a vast array of human cell types and are enriched in mutated regions of the genome that are closely associated with a broad spectrum of diseases.

Whitehead Institute researchers have determined that in basal breast cancer cells a transcription factor known as ZEB1 is held in a poised state, ready to increase the cells’ aggressiveness and enable them to transform into cancer stem cells capable of seeding new tumors throughout the body. Intriguingly, luminal breast cancer cells, which are associated with a much better clinical prognosis, carry this gene in a state in which it seems to be permanently shut down.