Long-term association of a transcription factor with its chromatin binding site can stabilize gene expression and cell fate commitment.

Proceedings of the National Academy of Sciences of the United States of America
J B GurdonNigel Garrett

Abstract

Some lineage-determining transcription factors are overwhelmingly important in directing embryonic cells to a particular differentiation pathway, such as Ascl1 for nerve. They also have an exceptionally strong ability to force cells to change from an unrelated pathway to one preferred by their action. Transcription factors are believed to have a very short residence time of only a few seconds on their specific DNA or chromatin-binding sites. We have developed a procedure in which DNA containing one copy of the binding site for the neural-inducing factor Ascl1 is injected directly into a Xenopus oocyte nucleus which has been preloaded with a limiting amount of the Ascl1 transcription factor protein. This is followed by a further injection of DNA as a competitor, either in a plasmid or in chromosomal DNA, containing the same binding site but with a different reporter. Importantly, expression of the reporter provides a measure of the function of the transcription factor in addition to its residence time. The same long residence time and resistance to competition are seen with the estrogen receptor and its DNA response elements. We find that in this nondividing oocyte, the nerve-inducing factor Ascl1 can remain bound to a specific ...Continue Reading

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Citations

Jan 12, 2021·Free Radical Biology & Medicine·Gareth W DavisonColum P Walsh
Jan 11, 2021·Current Opinion in Genetics & Development·Timothée Lionnet, Carl Wu
Mar 5, 2021·Journal of Animal Science and Biotechnology·Hee Jung ChoiJae Yong Han
Sep 28, 2020·Experimental Cell Research·J B GurdonH M Barbosa Triana
Apr 25, 2021·Experimental Eye Research·Ales Cvekl, Carolina Eliscovich
May 1, 2021·Developmental Biology·Michael W Klymkowsky
Mar 6, 2021·Annual Review of Plant Biology·Jose M AlvarezGloria M Coruzzi
Oct 2, 2021·Diabetes·Rafael Arrojo E Drigo
May 19, 2021·Cold Spring Harbor Perspectives in Biology·Feiyue Lu, Timothée Lionnet

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Methods Mentioned

BETA
ChIP
immunoprecipitation
in vitro transcription

Software Mentioned

MyoD

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