GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE289nnn/GSE289230/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289230GEOGSEfalseGATA3 Differentially Regulates the Transcriptome via Its Zinc Finger 2-Modulated Phase SeparationPhase separation (PS) underlies gene control by transcription factors. However, little is known about whether and how the DNA-binding domains (DBDs) regulate the PS for transcription factors to differentially regulate the transcriptome. The transcription factor GATA3, a master immune regulator, is frequently mutated in breast cancer. Here, we report that GATA3 undergoes its DBD-modulated PS to mediate the formation of chromatin condensates. We show that the DBD regulates the GATA3 PS through its zinc finger 2 (ZnF2), which provides positive charges for multivalent electrostatic interactions mainly via two arginine amino acids, R329 and R330. Breast cancer GATA3 with ZnF2-defective mutations, when compared to those without, cause aberrant ZnF2-modulated PS and condensates to remodel the differentially regulated transcriptome, resulting in a favorable prognosis for patients and reduced tumor growth in mice. Thus, GATA3 represents a principle of how a transcription factor differentially regulates the transcriptome via its DBD-modulated PS.2026/06/01GSE289230GSM8787394GSM8787393GSM8787392GSM8787391GSM8787390GSM8787389GSM8787388GSM8787387GSM8787397GSM8787386GSM8787396GSM878739524676289230Homo sapiens