Beyond On โand off:โค Research Reveals Graded Gene Expression inโ Cells
Forโข decades, theโฃ prevailing scientific understanding held โthat cells solidify their identity by fixing genes in eitherโค an “on” or โ”off” state through a process called DNA methylation. This mechanism โขwas believed to ensure cellularโค specialization, preventing โa skin cell, โfor instance, from transforming into a โคneuron.โ However,โ new research from MIT challenges this long-held “dogma,” demonstrating โthat cells can โคstably maintain gene expression at numerous points along a โฃspectrum, rather than being limited to binary states.
Domitilla Del โVecchio, a professor of mechanical and biological engineering at MIT, and her team observed this unexpectedโฃ phenomenon while engineering hamster ovarian cells to express a target gene at varying levels. Cells exhibited a rangeโข of activity – from brightโฃ fluorescence indicating high gene expression, to dim glows representing weaker โคexpression, andโ complete absence ofโข fluorescence โsignifying gene silencing.
Contrary to expectations,a shortโข burst of DNAโค methylation did โnot drive gene activity towards either extreme. Instead, cells โconsistently maintained their initial level of expression. Researchers observed a continuous spectrum of fluorescence intensity,confirming thatโ gene expression is “graded,” or analog,ratherโ than simply “on” or “off.”
This finding builds upon earlier hints of partial gene โexpression, previously considered a transient condition. the MIT team โdemonstrated โthat these intermediate โexpression levels โคcould persist for over five months, establishing their stability. sebastian Palacios, a lead โขauthor of theโฃ study, highlighted the surprise: “We found there โขwas a spectrum โขof โฃcells that expressed any โขlevel between on and off. And we thought,how is this possible?”
The โimplicationsโข of this โคdiscovery are significant.Del Vecchio suggests that cells may define their โidentity by locking genes at specific levels of expression, potentially revealing a far โขgreater diversityโ of cellโ types than currently recognized. This nuanced understanding couldโ be crucialโข in unravelingโค theโค complexitiesโฃ of health and โคdisease.
The research also โคoffers new perspectives on cancer and therapy resistance, โwhere cells’ โability to shiftโ states allowsโ themโข to evadeโ treatment. โคFurthermore, it provides synthetic biologistsโฃ with novel tools for precisely designing tissues and organs.Michaelโ Elowitz, a professor atโ Caltech unaffiliated with the study, lauded the work as demonstrating “how analog memory arises through chemical modifications toโ the DNA itself,” suggesting potential โforโค repurposing this natural โmechanism inโค synthetic biology.โฃ Palacios described theโข discovery as “mind-blowing,” anticipating its relevance across numerousโ biological processes.The research was supported by โfunding from the National โขScience Foundation,MODULUS,and a Vannevar Bush Faculty Fellowship through the โฃU.S. โฃOffice of Naval Research.
