Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Tuesday Speaker Abstracts

TEMPORAL DYNAMICS AND NUCLEATION OF Erα PHASE -SEPARATED CONDENSATES IN ESTROGEN SIGNALING Rajat Mann; National Centre for Biological Sciences, Bangalore, India Estrogen receptor- α (ERα) is a ligand -dependent transcription factor that regulates gene expression through enhancer binding, yet the dynamics of its chromatin occupancy and higher order organization remain incompletely understood. Here, we define the temporal and mechanistic principles of ERα clustering and condensate formation during early estrogen signalling. Genome- wide profiling revealed that ERα binds clustered sites within target loci as early as 5 minutes after estradiol (E2) stimulation, with binding intensity peaking at 10 minutes and stabilizing thereafter. Despite early ERα engagement, transcriptional activation of canonical targets such as TFF1 , NRIP1 , and GREB1 peaked later, coinciding with intra-TAD interactions and ERα -mediated chromatin looping. High- density ERα clusters displayed features of phase separated condensates, whose growth followed a nucleation-dependent trajectory. We identify FOXA1 as a critical nucleator: ERα -persistent sites enriched for FOXA1 motifs pre-mark clustered enhancers prior to signalling , and FOXA1 loss severely compromised ERα condensate assembly. Conversely, breast cancer–associated wing2 domain mutations in FOXA1 induced aberrant nucleation, leading to excessive ERα condensates and ectopic chromatin opening at noncanonical sites. Toget her, our results establish a temporal framework for ERα binding and condensate formation, uncover FOXA1 as an essential nucleator of ERα phase separation, and reveal how oncogenic FOXA1 mutations reprogram ERα -dependent enhancer networks. CONNECTING ACTIVE CHROMATIN FOLDING PROPERTIES FROM NUCLEOSOME SCALE TO WHOLE-CHROMOSOME SCALE Ranjith Padinhateeri ; 1 IIT Bombay, Mumbai, India Active chromatin folding encodes additional layers of information that regulate gene activation and repression in a time-dependent manner. This folding spans multiple length scales — from the nucleosome to the entire chromosome — across several orders of magnitude. We will present physics-based models to understand chromatin folding and predict its properties across these scales. Additionally, we will discuss how active folding influences key biological processes such as DNA repair, gene regulation, and DNA packaging.

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