02581nas a2200277   4500008004100000022001400041245008100055210006900136260000800205300001100213490000800224520174600232653000901978653001401987653001502001653001502016653002302031653001202054653001102066100002202077700002602099700002102125700002402146700002002170856011302190       2026                        eng d  a0006-291X00aRecognition of diverse GATA motifs necessitates multimodal GATA3-DNA binding0 aRecognition of diverse GATA motifs necessitates multimodal GATA3  cJUN  a1537180 v8173 a<p>
	GATA3 is a pioneer transcription factor that plays a central role in the formation, proliferation, and sustenance of various immune cell types, notably serving as the ``master regulator'' of T helper 2 (Th2) cell differentiation. It regulates gene expression by recognizing the canonical DNA consensus motif (A/T)GATA(A/G) through its highly conserved zinc finger domains. However, beyond this classical binding motif, emerging evidence indicates that GATA3 also recognizes a varied array of noncanonical and palindromic sequence motifs, but the underlying molecular mechanisms are unclear. In this review, we discuss an emerging aspect of GATA3 function that links these diverse DNA sequence motifs to varying structural binding modes and finally to differential chromatin outcomes. We discuss how the alternative sequence motifs may engage the two zinc finger domains differently, leading towards a multitude of binding modes underlying this diverse motif recognition. The spacer length between the GATA motifs has been shown to modulate DNA binding and the geometric constraints imposed may help determine the binding mode. We reanalyzed previous data and show that these diverse motifs, as well as the spacers, modulate nucleosomal outcomes, highlighting the importance of these motifs in GATA3 function. Several disease-associated mutations, such as those implicated in autoimmune diseases and cancer, have been reported for GATA3, and we discuss how these mutations alter the binding of the zinc finger domains. This link between sequence recognition and DNA binding modes represents an underexplored aspect of GATA3 function that is necessary for understanding its multifaceted regulatory role in human health and disease.</p>
10aGATA10aMutations10aNucleosome10aPalindrome10aReverse palindrome10aSpacers10aTandem1 aGharui, Sowmomita1 aPuntambekar, Shraddha1 aSarkar, Ram, Rup1 aNarlikar, Leelavati1 aSengupta, Durba  uhttps://library.ncl.res.in/content/recognition-diverse-gata-motifs-necessitates-multimodal-gata3-dna-binding