Studies of the Molecular Features of Brd4-Nut and P300 That Contribute to Condensate Formation and Transcriptional Regulation

Aberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein Brd4-Nut drives aberrant gene expression and forms condensates in Nut Carcinoma (NC). It has not been clear how these condensates form and whether they modulate gene expression. Here, I dissected the molecular features of Brd4-Nut and a histone acetyltransferase (HAT), p300, and analyzed their contribution to condensate formation and transcriptional changes. I determined that a minimal fragment of Nut (MIN) in fusion with Brd4 is necessary and sufficient for binding to p300, and for condensate formation. A Brd4-p300 fusion protein also forms condensates and drives a transcriptional profile similar to Brd4-Nut(MIN). The intrinsically disordered regions, transcription factor - binding domains, and HAT activity of p300 all collectively contribute to condensate formation. Conversely, only HAT activity appears to be necessary to mimic the transcriptional profile of cells expressing Brd4-Nut. My results suggest that interaction of Brd4-Nut with p300 is important for aberrant condensate formation, and that multiple, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation.

Author dc:creator

• Kosno, Martyna Olga

Contributors dc:contributor

• Kohler, Jennifer J.
• Tu, Benjamin
• Henne, W. Mike
• Brekken, Rolf A.
• Liszczak, Glen
• Rosen, Michael K.

• Carcinoma, Squamous Cell
• Cell Cycle Proteins
• E1A-Associated p300 Protein
• Gene Expression Regulation, Neoplastic
• Transcription Factors

Language dc:language

en

Identifier

1381370396

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/10069