474B Poster - 06. Regulation of gene expression
Friday April 08, 2:00 PM - 4:00 PM

Investigating the role of intrinsic protein disorder in transcription factor dynamics and function


Authors:
Colleen Hannon 1; Michael Eisen 1,2

Affiliations:
1) University of California, Berkeley, Berkeley, CA; 2) Howard Hughes Medical Institute, Berkeley, CA

Keywords:
c. activators/coactivators; d. repressors/corepressors

Modern microscopy has revealed that core nuclear functions, including transcription, replication, and heterochromatin formation occur in spatially restricted clusters. Our lab is investigating the role that the sub-nuclear localization of transcription factors, target DNA sequences and transcriptional machinery plays in regulating RNA synthesis in the early Drosophila embryo. A nearly ubiquitous feature of eukaryotic transcription factors (TFs) is tracts of low complexity amino acid sequence, which result in intrinsically disordered regions (IDRs) within the protein. It has been proposed IDR-containing TFs mediate the co-localization of transcriptional machinery and target genes. However relatively little is known about the contribution of IDRs to TF localization, molecular interactions, and transcriptional activation. Using a novel algorithm to identify IDRs in the Drosophila proteome, we designed a library of IDRs from TFs expressed in the early Drosophila embryo. We used this library to conduct a broad survey of the nuclear sub-localization of TFs, using a high throughput imaging screen in Drosophila S2 cells. We found that while subnuclear clustering does not occur when the IDRs are expressed alone, it is frequently seen in full length TFs. These results are consistent in Drosophila embryos, suggesting that IDRs are insufficient to drive the sub-nuclear clustering behavior of transcription factors.