02232nas a2200229   4500008004100000022001400041245007800055210006900133260000800202300001200210490000700222520147600229653002901705653001701734653003501751653002401786653002401810653002501834100002201859700002001881856010101901       2025                        eng d  a0887-358500aMolecular interactions of the pioneer transcription factor GATA3 With DNA0 aMolecular interactions of the pioneer transcription factor GATA3  cFEB  a555-5660 v933 a<p>
	The GATA3 transcription factor is a pioneer transcription factor that is critical in the development, proliferation, and maintenance of several immune cell types. Identifying the detailed conformational dynamics and interactions of this transcription factor, as well as its clinically important population variants will allow us to unravel its mode of action. In this study, we analyze the molecular interactions of the GATA3 transcription factor bound to dsDNA as well as three clinically important population variants by atomistic molecular dynamics simulations. We identify the effect of the variants on the DNA conformational dynamics and delineate the differences compared to the wildtype transcription factor that could be related to impaired function. We highlight the structural plasticity in the binding of the GATA3 transcription factor and identify important DNA-protein contacts. Although the DNA-protein contacts are persistent and appear to be stable, they exhibit nanosecond timescale fluctuations and several binding/unbinding events. Further, we identify differential DNA binding in the three variants and show that the N-terminal binding is reduced in two of the variants. Our results indicate that reduced minor groove width and DNA diameter are important hallmarks for the binding of GATA3. Our work is an important step towards understanding the functional dynamics of the GATA3 protein and its clinically significant population variants.</p>
10aDNA-protein interactions10aGATA protein10aMolecular dynamics simulations10amolecular mechanism10apopulation variants10atranscription factor1 aGharui, Sowmomita1 aSengupta, Durba  uhttps://library.ncl.res.in/content/molecular-interactions-pioneer-transcription-factor-gata3-dna