Sox9 and p300 cooperatively regulate chromatin-mediated transcription (JBC, Published on August 18, 2005)

報告日期: 2005/11/01
報告時間: 16:00/16:50
報告學生: 呂淳雯
講評老師: 洪建中

Sox9 and p300 cooperatively regulate chromatin-mediated transcription

J Biol Chem. 2005 Oct 21; 280(42):35203-8


Speaker: 呂淳雯                              Time: 11/02/2005 16:00-16:50

Commentator: 洪建中 老師                               Place: Room 602


Chondrocytes differentiation, a multi-step pathway during which mesenchymal stem cells (MSCs) differentiate into chondrocytes. SOX9 (SRY-type high mobility group box 9), which is a high-mobility group (HMG) domain transcription factor, plays an essential role in chondrocyte differentiation and chondrocyte-specific genes expression. The a1 chain of type II collagen, which is encoded by the Col2a1 gene, is the major component of cartilage extracellular matrix. Col2a1 expression is regulated by Sox9 through binding to the enhancer region of Col2a1. Previously the authors found that CBP/p300 was an important co-activator for enhancing the transcriptional activity of Sox9. CBP/p300 appeared to promote transcriptional activation, in part via their association with RNA polymerase II complexes and via intrinsic histone acetyltransferase (HAT) activities that destabilized the higher-order structure of nucleosomal arrays. However, the precise mechanism by which CBP/p300 facilitates Sox9-mediated transcription was not clear. In this study using a chromatinized target gene, which was reconstituted with histones in vitro, revealed that Sox9 and p300 cooperatively activated the chromatin-mediated transcription. In addition both p300 and Sox9 synergistically acetylated histones on a chromatinized DNA. Stimulating chondrocytes with histone deacetylase inhibitor trichostatin A (TSA) increased the binding of acetylated histone H3/H4 around the Col2a1 enhancer region and the expression of Col2a1 and Sox9-regulated cartilage matrix genes. Therefore, these findings suggested that p300 and Sox9 synergistically activated transcription via p300 acetylated histones on chromatinized DNA.



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