Transcription factor occupancy in differentiating skeletal muscle

With recent advances in high-throughput sequencing, mapping of genome-wide transcription factor occupancy has become feasible. To advance the understanding of skeletal muscle differentiation specifically and transcriptional regulation in general, I determined the genome-wide occupancy map for myogenin in differentiating C2C12 myocyte cells. I then analyzed the myogenin map for underlying sequence content and the association between occupied elements and expression trajectories of adjacent genes. Having determined that myogenin primarily associates with expressed genes, I performed a similar analysis on occupancy maps of other transcription factors active during skeletal muscle differentiation, including an extensive analysis of co-occupancy. This analysis provided strong motif evidence for protein-protein interactions as the primary driving force in the formation of Myogenin / Mef2 and MyoD / AP-1 complexes at jointly-occupied sites. Finally, factor occupancy analysis was extended to include bHLH transcription factors in tissues other than skeletal muscle. The cross-tissue analysis led to the emergence of a motif structure used by bHLH TFs to encode either tissue-specific or "general" (public) access in a variety of lineages.

Analysis of temporal structure in spike trains of visual cortical area MT

The temporal structure of neuronal spike trains in the visual cortex can provide detailed information about the stimulus and about the neuronal implementation of visual processing. Spike trains recorded from the macaque motion area MT in previous studies (Newsome et al., 1989a; Britten et al., 1992; Zohary et al., 1994) are analyzed here in the context of the dynamic random dot stimulus which was used to evoke them. If the stimulus is incoherent, the spike trains can be highly modulated and precisely locked in time to the stimulus. In contrast, the coherent motion stimulus creates little or no temporal modulation and allows us to study patterns in the spike train that may be intrinsic to the cortical circuitry in area MT. Long gaps in the spike train evoked by the preferred direction motion stimulus are found, and they appear to be symmetrical to bursts in the response to the anti-preferred direction of motion. A novel cross-correlation technique is used to establish that the gaps are correlated between pairs of neurons. Temporal modulation is also found in psychophysical experiments using a modified stimulus. A model is made that can account for the temporal modulation in terms of the computational theory of biological image motion processing. A frequency domain analysis of the stimulus reveals that it contains a repeated power spectrum that may account for psychophysical and electrophysiological observations.

Some neurons tend to fire bursts of action potentials while others avoid burst firing. Using numerical and analytical models of spike trains as Poisson processes with the addition of refractory periods and bursting, we are able to account for peaks in the power spectrum near 40 Hz without assuming the existence of an underlying oscillatory signal. A preliminary examination of the local field potential reveals that stimulus-locked oscillation appears briefly at the beginning of the trial.