Biology subjects

Terry, B.

Publications and source records attributed to Terry, B..

3 recordsLinked to original sources

bioRxiv2026

Dynamic TET1 repression coordinates activation of macroH2A.2-poised bivalent genes during neuroectoderm differentiation

Cell state transitions involve changes in gene expression programs in conjunction with epigenetic regulation occurring in chromatin. Bivalent chromatin, marked by overlapping active H3K4me3 and repressive H3K27me3, poises key developmental genes during pluripotency for cell type-specific activation during differentiation. However, the molecular mechanisms that activate bivalent genes during lineage commitment remain poorly understood. Here, we elucidate how the cytosine dioxygenase TET1 promotes neuroectoderm differentiation through dynamic chromatin binding and a non-catalytic repressor function. Through a hypothesis-free screen for TET1 chromatin complex partners, we find that TET1 physically interacts with macroH2A.2 and H2A.X on chromatin. Integrated multi-omic analyses reveal that the non-catalytic repressor function of TET1 and a novel activating function of the H2A variant macroH2A.2 together promote a poised transcriptional state within bivalent chromatin during pluripotency. Upon pluripotency exit, TET1 disengages from macroH2A.2-marked early neuroectoderm genes to permit their activation, while remaining bound as a repressor at mesoendoderm and late neural genes to prevent alternative cell state transitions. Furthermore, TET1 retention at accessible primed enhancers supports neural program activation. Together, our findings reveal a noncanonical functional interplay within bivalent chromatin between TET1 and macroH2A.2 that maintains a poised state during pluripotency and predicts selective gene activation during neuroectoderm specification.

developmental biology↗

bioRxiv2026

Brainwide representation of navigation

Tracking your position in the environment during navigation requires integrating multiple signals into a spatial representation. This process is thought to occur primarily in the hippocampal formation, but evidence for it has also been observed in other regions. To investigate it across the brain, we recorded from over 20,000 neurons in mice navigating a virtual corridor that decoupled position from correlated signals. Spatial position was encoded in every region, and was more common in neurons tuned to visual landmarks. Most neurons brainwide were also modulated by running speed, likely reflecting arousal, and many by rewards. The hippocampal formation represented spatial position slightly more uniformly than other regions, but less precisely than visual cortex. Spatial position and other navigational signals are thus represented widely across the brain.

neuroscience↗

bioRxiv2024

Dorsal prefrontal cortex drives perseverative behavior in mice

Perseveration - repeating one choice when others would generate larger rewards - is a common behavior, but neither its purpose nor neuronal mechanisms are understood. Here we demonstrate a neural correlate and causal role of dorsal prefrontal cortex, specifically anterior supplementary motor cortex (MOs) in perseveration in mice performing a dynamic reward learning task. An auditory go cue signaled mice to turn a wheel either left or right, with the reward probability of each action switching in blocks. Mice perseverated, gaining suboptimal reward, but were faster when making repeated choices. Neuropixels recordings found neurons whose activity correlated with perseveration and predicted rapid reaction times, almost exclusively in anterior MOs. Optogenetically inhibiting this region at choice time reduced perseveration and slowed reactions. In contrast, inactivating medial prefrontal cortex at choice time had no effect, but inactivating it after reward delivery impaired learning. In this task, therefore, anterior MOs reflects a perseverative decision variable, and is necessary for mediating the effect of this decision variable on choice and reaction time.

neuroscience↗