Title

Identification of neocortical proteins that interact with the transcription factor Sp8

Presenter Information

Michael Mullan

Document Type

Oral Presentation

Location

SURC 202

Start Date

17-5-2012

End Date

17-5-2012

Abstract

The neocortex is the mammalian brain structure that mediates conscious decision making and actions. This structure initially appears homogenous but is divided into functionally and architecturally distinct areas by a process called neocortical arealization. Neocortical arealization is mediated by several key transcription factors, proteins that control when genes are turned on or off, including the zinc finger protein Sp8. Sp8 is differentially produced within the embryonic neocortex; high levels of Sp8 are present in the anterior aspect of the neocortex, where it induces the motor area, while gradually reduced levels of Sp8 are found while examining areas more and more posterior. The mechanism through which this smooth gradient of Sp8 is converted into different areas with distinct boundaries remains undetermined. The ability of Sp8 to regulate its target genes is therefore likely assisted by interactions with additional neocortical proteins. To initiate experiments that will test this hypothesis, we have conducted a yeast two-hybrid screen to identify binding partners for Sp8. This technique has revealed several candidate Sp8-binding proteins, including Polyubiquitin-C (Ubc), PCNA, rRNA binding protein and ribosomal protein S20. Ubc is an ubiquitin-activating enzyme that indirectly interacts with a larger CCR4-Cnot complex and regulates the modification of other proteins. One job of the multifunctional CCR4-Cnot complex is to control genes by modifying chromatin or other gene-regulating proteins. Thus, we hypothesize that the Sp8-Ubc interaction mediates the formation of a complex containing Sp8 and the CCR4-Cnot complex to regulate gene expression patterns, and thus boundary formation, within the developing neocortex.

Faculty Mentor(s)

Todd Kroll

Additional Mentoring Department

Chemistry

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Identification of neocortical proteins that interact with the transcription factor Sp8

SURC 202

The neocortex is the mammalian brain structure that mediates conscious decision making and actions. This structure initially appears homogenous but is divided into functionally and architecturally distinct areas by a process called neocortical arealization. Neocortical arealization is mediated by several key transcription factors, proteins that control when genes are turned on or off, including the zinc finger protein Sp8. Sp8 is differentially produced within the embryonic neocortex; high levels of Sp8 are present in the anterior aspect of the neocortex, where it induces the motor area, while gradually reduced levels of Sp8 are found while examining areas more and more posterior. The mechanism through which this smooth gradient of Sp8 is converted into different areas with distinct boundaries remains undetermined. The ability of Sp8 to regulate its target genes is therefore likely assisted by interactions with additional neocortical proteins. To initiate experiments that will test this hypothesis, we have conducted a yeast two-hybrid screen to identify binding partners for Sp8. This technique has revealed several candidate Sp8-binding proteins, including Polyubiquitin-C (Ubc), PCNA, rRNA binding protein and ribosomal protein S20. Ubc is an ubiquitin-activating enzyme that indirectly interacts with a larger CCR4-Cnot complex and regulates the modification of other proteins. One job of the multifunctional CCR4-Cnot complex is to control genes by modifying chromatin or other gene-regulating proteins. Thus, we hypothesize that the Sp8-Ubc interaction mediates the formation of a complex containing Sp8 and the CCR4-Cnot complex to regulate gene expression patterns, and thus boundary formation, within the developing neocortex.