Physical Model of p300 Acetyltransferase and Bromodomain (LB89)

Abstract

In the nucleus of a cell, chromatin is structured into nucleosomes in which the DNA is wrapped around a histone core, condensing the DNA. In this form, DNA is not readily accessible for gene expression. Post‐translational modification to the histone proteins, such as acetylation, regulates gene expression. Histone acetyltranferase (HAT) catlyzes the transfer of an acetyl group to a target lysine by aligning an acetyl‐CoA group with a lysine on the unstructured histone tail region. The acetylated lysine tail then becomes a binding site for other factors. Bromodomain‐containing proteins (BRD) recognize and bind to the acetylated lysine and recruit transcription factors and RNA polymerase II complex to the DNA. The transcriptional coactivator p300 contains both a HAT and BRD region and is known to play an important role in cell cycle and tumor suppression. The activity of the p300 HAT is in part dependent upon the activity of its BRD, and disruption of the BRD can significantly affect transcription of p300‐regulated gene targets. The Hostos‐Lincoln Academy SMART (Students Modeling A Research Topic)Team has generated models of both the HAT (3biy.pdb) and BRD (3i3j.pdb) of p300 using 3D printing technology to illustrate the interplay between HAT and BRD in the transcription of p300 genes.Grant Funding Source: Supported by grants from the NIH‐SEPA and NIH‐CTSA.