- 2008. University of Würzburg (Germany). PhD.
The cis-regulatory architecture underlying subtype-specific rhodopsin expression
A cis-regulatory element (CRE) is a noncoding DNA region that controls where, when, and how strongly a gene is expressed. Identifying CREs and unraveling their architecture are fundamental problems in molecular biology. I am interested in the regulatory mechanisms that generate the complex expression patterns of rhodopsins in particular photoreceptor subtypes (Fig. 1A), which is critical for color vision.
Rhodopsins are particularly suited for a cis-regulatory analysis, as their expression is mainly mediated on the transcriptional level and compact CREs of less than 300 base pairs upstream of the transcription start site are sufficient to reproduce their expression patterns. Despite significant progress in identifying key transcriptional activators and repressors that control spatiotemporal rhodopsin expression, it is still poorly understood how the combinatorial input of these trans-acting factors is integrated on the CREs.
To gain insights into the underlying regulatory logic, we performed an extensive structure-function analysis complemented by phylogenetic footprinting. We identified key regulatory motifs and found that single base pairs in highly conserved motifs are critical for proper subtype-specific expression. Moreover, as some rhodopsins are not only expressed in the adult retina (Fig. 1B), but also in the larval eye, we are able to compare the cis-regulatory 'grammar' in different cellular and developmental contexts (in collaboration with Simon Sprecher, Fribourg). Finally, to test the sufficiency of the identified motifs and to reconstruct rhodopsin regulation, we are using artificial binding sites to reverse-engineer synthetic rhodopsin promoters.
Fig. 1 A) Stochastic and mutually exclusive expression of Rh5 (blue)
and Rh6 (red). A cis-regulatory element drives expression of a GFP
reporter (green) in a pattern that overlaps with the one of Rh6.
B) Dissected adult fly retinas (picture from reference #2, see below).
- K99 Pathway to Independence Award, NIH/NEI - Current
- DFG (Deutsche Forschungsgemeinschaft)
- European Molecular Biology Organization (EMBO) Long-term Fellowship
- 1) Rister, J., Razzaq, A., Boodram, P., Desai, N., Tsanis, C., Chen, H., Jukam, D., and Desplan, C.
Single base pair differences in a shared motif determine differential Rhodopsin expression.
Science 360, 6265, 1258-1261. (2015). PMID: 26785491.
- 2) David Jukam*, Baotong Xie*, Jens Rister*, David Terrell, Mark Charlton-Perkins, Daniela Pistillo, Brian Gebelein, Claude Desplan, Tiffany Cook.
Opposite Feedbacks in the Hippo Pathway for Growth Control and Neural Fate.
Science (2013). PMID: 23989952. *These authors contributed equally.
- 3) Rister, J., Desplan, C. and Vasiliauskas, D.
Establishing and maintaining gene expression patterns: insights from sensory receptor patterning.
Development 140(3) 493-503. doi:10.1242/dev.079095. (2013).
- 4) Hsiao, H. Y.*, Johnston Jr., R. J.*, Jukam, D.*, Vasiliauskas, D.*, Desplan, C., Rister, J.
Dissection and Immunohistochemistry of Larval, Pupal and Adult Drosophila Retinas.
J. Vis. Exp. (69), e4347, doi:10.3791/4347 (2012). *These authors contributed equally. [WEB]
- 5) Rister, J. and Desplan, C.
The retinal mosaics of opsin expression in invertebrates and vertebrates. .
Develop. Neurobiol., 71(12) 1212-26 (2011). PMID: 21557510.
- 6) Rister, J. and Desplan, C.
Deciphering the genome's regulatory code: The many languages of DNA.
BioEssays 32, (5) (2010). PMCID: PMC3024831.
- 7) Rister, J., Pauls, D., Schnell, B., Ting, C.-Y., Lee, C.-H.,
Sinakevitch, I., Morante, J., Strausfeld, N. J., Ito, K. and Heisenberg, M.
Dissection of the peripheral motion channel in the visual system of Drosophila melanogaster.
Neuron 56, 155-170. (2007).
- 8) Rister, J., and Heisenberg, M.
Distinct functions of neuronal synaptobrevin in developing and mature fly photoreceptors.
J Neurobiol 66, 1271-1284. (2006).