Hirose, S. | bioRxiv Science

bioRxiv2018

A stochastic epigenetic switch controls the dynamics of T-cell lineage commitment

Cell fate decisions occur through the switch-like, irreversible activation of fate-specifying genes. These activation events are often assumed to be tightly-coupled to changes in upstream transcription factors, but could also be constrained by cis-epigenetic mechanisms at individual gene loci. Here, we studied the activation of Bcl11b, which controls T-cell fate commitment. To disentangle cis and trans effects, we generated mice where two Bcl11b copies are tagged with distinguishable fluorescent proteins. Quantitative live microscopy of progenitors from these mice revealed that Bcl11b turned on after a stochastic delay averaging multiple days, which varied not only between cells but also between Bcl11b alleles within the same cell. Genetic perturbations, together with mathematical modeling, showed that a distal enhancer controls the rate of epigenetic activation, while a parallel Notch-dependent trans-acting step stimulates expression from activated loci. These results show that developmental fate transitions can be controlled by stochastic cis-acting events on individual loci.

bioinformatics↗

bioRxiv2018

Cortical activation associated with motor preparation can be used to predict the freely chosen effector of an upcoming movement and reflects response time: An fMRI decoding study

Motor action is prepared in the human brain for rapid initiation at the appropriate time. Recent non-invasive decoding techniques have shown that brain activity for action preparation represents various parameters of an upcoming action. In the present study, we demonstrated that a freely chosen effector can be predicted from brain activity measured using functional magnetic resonance imaging (fMRI) before initiation of the action. Furthermore, the activity was related to response time (RT). We measured brain activity with fMRI while 12 participants performed a finger-tapping task using either the left or right hand, which was freely chosen by them. Using fMRI decoding, we identified brain regions in which activity during the preparatory period could predict the hand used for the upcoming action. We subsequently evaluated the relationship between brain activity and the RT of the upcoming action to determine whether correct decoding was associated with short RT. We observed that activity in the supplementary motor area, dorsal premotor cortex, and primary motor cortex measured before action execution predicted the hand used to perform the action with significantly above-chance accuracy (approximately 70%). Furthermore, in most participants, the RT was shorter in trials for which the used hand was correctly predicted. The present study showed that preparatory activity in cortical motor areas represents information about the effector used for an upcoming action, and that well-formed motor representations in these regions are associated with reduced response times.\n\nHighlightsO_LIBrain activity measured by fMRI was used to predict freely chosen effectors.\nC_LIO_LIM1/PMd and SMA activity predicted the effector hand prior to action initiation.\nC_LIO_LIResponse time was shorter in trials in which effector hand was correctly predicted.\nC_LIO_LIFreely chosen action is represented in the M1/PMd and SMA.\nC_LIO_LIWell-formed preparatory motor representations lead to reduced response time.\nC_LI

neuroscience↗