Biology subjects

Badayeva, Y.

Publications and source records attributed to Badayeva, Y..

3 recordsLinked to original sources

bioRxiv2026

SMFnet reveals principles of combinatorial transcription factor assembly

Combinatorial assembly of transcription factors (TFs) opens chromatin at cis-regulatory elements (cREs) to establish cell-type-specific gene expression. Dissecting the role of individual TFs and their collective function has been limited by the diversity of TF binding-site arrangements across cREs. A single regulatory sequence can support multiple configurations of TF and nucleosome occupancy, raising the possibility that distinct chromatin states reflect different TF assemblies. Predictive models linking regulatory sequence to chromatin accessibility collapse these distinct molecular states into population averages, obscuring how TF assemblies shape accessible chromatin. Here, we introduce SMFNet, a generative diffusion model that predicts distributions of single-molecule chromatin accessibility profiles from DNA sequence, and PRISM, which identifies sequence features associated with individual molecular states. Together, these approaches enable us to systematically associate single molecule chromatin states at cREs with specific TF binding motifs. Experimental perturbation of these motifs redistributes the corresponding states as predicted by SMFNet, supporting their interpretation as TF-dependent configurations underlying chromatin opening. We then use controlled in silico motif screens to systematically dissect individual and combinatorial TF contributions to chromatin opening. Individual TFs show distinct chromatin-opening signatures, differing in accessible-region width and nucleosome-positioning precision even when associated with similar levels of chromatin accessibility. Combining motifs reveals partner- and spacing-dependent effects on chromatin accessibility, TF occupancy and nucleosome positioning. Genetic perturbation of TF binding sites using natural variation at endogenous cRE confirms that TF-specific properties shape chromatin accessibility in vivo. Together, our findings reveal sequence-encoded principles of combinatorial TF assembly during chromatin opening.

genetics↗

bioRxiv2024

Freely foraging macaques value information in ambiguous terrains

Among non-human primates, macaques are recognized for thriving in a wide range of novel environments. Previous studies show macaques affinity for new information. However, little is known about how information-seeking manifests in their spatial navigation pattern in ambiguous foraging terrains, where the location and distribution of the food are unknown. We investigated the spatial pattern of foraging in free-moving macaques in an ambiguous terrain, lacking sensory cues about the reward distribution. Rewards were hidden in a uniform grid of woodchip piles spread over a 15 sqm open terrain and spatially distributed according to different patchy distributions. We observed Levy-like random walks in macaques spatial search pattern, balancing relocation effort with exploration. Encountering rewards altered the foraging path to favor the vicinity of discovered rewards temporarily, without preventing longer-distance travels. These results point toward continuous exploration, suggesting that explicit information-seeking is a part of macaques foraging strategy. We further quantified the role of information seeking using a kernel-based model, combining a map of ambiguity, promoting information seeking, with a map of discovered rewards and a map of proximity. Fitting this model to the foraging paths of our macaques revealed individual differences in their relative preference for information, reward, or proximity. The model predicted that a balanced contribution of all three factors performs and adapts to an ambiguous terrain with semi-scattered rewards, a prediction we confirmed using further experimental evidence. We postulate an explicit role for seeking information as a valuable entity to reduce ambiguity in macaques foraging strategies, suggesting an ecologically valid way of foraging ambiguous terrains. Author SummaryIn a novel and ambiguous terrain lacking sensory information about the location or distribution of food, foragers obtain information by sampling. This process is crucial for animals thriving in a new habitat. We allowed free-roaming macaques to forage at their own pace in a controlled terrain to which they had limited prior exposure. Based on their foraging paths, we developed a computational model representing an individuals drive for reward-seeking, information-seeking, or energy preservation. These drives were represented as superimposing maps from the foragers perspective. We found that information-seeking, continuous exploration of unknown areas, is crucial for foraging under ambiguity. This finding is consistent with a theory suggesting that animals, specifically humans and other primates, seek information to reduce their uncertainty about the environment. Our study suggests that the statistical properties of primates random foraging patterns reveal their complex decision-making process, including adaptation to novel environments.

animal behavior and cognition↗

bioRxiv2021

Temporal analysis of enhancers during mouse brain development reveals dynamic regulatory function and identifies novel regulators of cerebellar development.

In this study, we identified active enhancers in the mouse cerebellum at embryonic and postnatal stages establishing the first catalog of enhancers active during embryonic cerebellum development. The majority of cerebellar enhancers have dynamic activity between embryonic and postnatal development. Cerebellar enhancers were enriched for neural transcription factor binding sites with temporally specific expression. Putative gene targets displayed spatially restricted expression patterns, indicating cell-type specific expression regulation. Functional analysis of target genes indicated that enhancers regulate processes spanning several developmental epochs such as specification, differentiation and maturation. We use these analyses to discover one novel regulator and one novel marker of cerebellar development: Bhlhe22 and Pax3, respectively. We identified an enrichment of de novo mutations and variants associated with autism spectrum disorder in cerebellar enhancers. Our study provides insight into the dynamics of gene expression regulation by enhancers in the developing brain and delivers a rich resource of novel gene-enhancer associations providing a basis for future in-depth studies in the cerebellum.

neuroscience↗