Transcriptional Coactivator PC4, a Chromatin-Associated Protein, Induces Chromatin Condensation

Abstract

Human transcriptional coactivator PC4 is a highly abundant multifunctional protein which plays diverse important roles in cellular processes, including transcription, replication, and repair. It is also a unique activator of p53 function. Here we report that PC4 is a bona fide component of chromatin with distinct chromatin organization ability. PC4 is predominantly associated with the chromatin throughout the stages of cell cycle and is broadly distributed on the mitotic chromosome arms in a punctate manner except for the centromere. It selectively interacts with core histones H3 and H2B; this interaction is essential for PC4-mediated chromatin condensation, as demonstrated by micrococcal nuclease (MNase) accessibility assays, circular dichroism spectroscopy, and atomic force microscopy (AFM). The AFM images show that PC4 compacts the 100-kb reconstituted chromatin distinctly compared to the results seen with the linker histone H1. Silencing of PC4 expression in HeLa cells results in chromatin decompaction, as evidenced by the increase in MNase accessibility. Knocking down of PC4 up-regulates several genes, leading to the G 2 /M checkpoint arrest of cell cycle, which suggests its physiological role as a chromatin-compacting protein. These results establish PC4 as a new member of chromatin-associated protein family, which plays an important role in chromatin organization.

Activation of p53 Function by Human Transcriptional Coactivator PC4: Role of Protein-Protein Interaction, DNA Bending, and Posttranslational Modifications

“…It plays an important role in transcription, replication, DNA repair, and normal cellular growth (12,20,35,41). Recently we have found that PC4 is a chromatin-associated protein and is important for chromatin organization and cell cycle progression (9). PC4 is phosphorylated by CKII and acetylated by p300.…”

Human positive coactivator 4 is a potential novel therapeutic target in non-small cell lung cancer

“…[9][10][11][12][13] It is a member of chromatinassociated protein superfamily and has a critical role in chromatin organization. 14 Studies have reported that PC4 could activate p53 activity as well as a responsive gene of p53. [15][16][17] PC4 was also shown to restore AP-2 activity and suppress ras-induced transformation.…”

Genome-wide location analysis reveals a role for Sub1 in RNA polymerase III transcription

“…Both PC4 and Sub1 were recently shown to play a negative role in Pol II transcription in vivo. Knocking down PC4 expression using siRNA altered the expression of less than 200 genes, most of them being upregulated (14), whereas disruption of SUB1 increased IMD2 transcription (38) showing that PC4/Sub1 could also repress the expression of some genes under normal growth conditions. Like the NC2 cofactor (39) or Mot1 (40), Sub1 may thus play both a positive and a negative role in transcription.…”