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2 Janelia Publications

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    03/08/19 | Neural evolution of context-dependent fly song.
    Ding Y, Lillvis JL, Cande J, Berman GJ, Arthur BJ, Long X, Xu M, Dickson BJ, Stern DL
    Current Biology : CB. 2019 Mar 08;29(7):1089-99. doi: 10.1016/j.cub.2019.02.019

    It is unclear where in the nervous system evolutionary changes tend to occur. To localize the source of neural evolution that has generated divergent behaviors, we developed a new approach to label and functionally manipulate homologous neurons across Drosophila species. We examined homologous descending neurons that drive courtship song in two species that sing divergent song types and localized relevant evolutionary changes in circuit function downstream of the intrinsic physiology of these descending neurons. This evolutionary change causes different species to produce divergent motor patterns in similar social contexts. Artificial stimulation of these descending neurons drives multiple song types, suggesting that multifunctional properties of song circuits may facilitate rapid evolution of song types.

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    11/02/17 | Nuclear microenvironments modulate transcription from low-affinity enhancers.
    Tsai A, Muthusamy AK, Alves MR, Lavis LD, Singer RH, Stern DL, Crocker J
    eLife. 2017 Nov 02;6:. doi: 10.7554/eLife.28975

    Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogastershavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity of svb enhancers revealed an inverse relationship between enhancer affinity and Ubx concentration required for transcriptional activation. The Ubx cofactor, Homothorax (Hth), was co-enriched with Ubx near enhancers that require Hth, even though Ubx and Hth did not co-localize throughout the nucleus. Thus, microenvironments of high local transcription factor and cofactor concentrations could help low-affinity sites overcome their kinetic inefficiency. Mechanisms that generate these microenvironments could be a general feature of eukaryotic transcriptional regulation.

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