Department of Cell and Developmental Biology, University of Illinois, Urbana, IL 61801, USA.
J Cell Sci. 2011 Sep 15;124(Pt 18):3149-63. doi: 10.1242/jcs.086603.
In eukaryotes, higher order chromatin structure governs crucial cellular processes including DNA replication, transcription and post-transcriptional gene regulation. Specific chromatin-interacting proteins play vital roles in the maintenance of chromatin structure. We have identified BEND3, a quadruple BEN domain-containing protein that is highly conserved amongst vertebrates. BEND3 colocalizes with HP1 and H3 trimethylated at K9 at heterochromatic regions in mammalian cells. Using an in vivo gene locus, we have been able to demonstrate that BEND3 associates with the locus only when it is heterochromatic and dissociates upon activation of transcription. Furthermore, tethering BEND3 inhibits transcription from the locus, indicating that BEND3 is involved in transcriptional repression through its interaction with histone deacetylases and Sall4, a transcription repressor. We further demonstrate that BEND3 is SUMOylated and that such modifications are essential for its role in transcriptional repression. Finally, overexpression of BEND3 causes premature chromatin condensation and extensive heterochromatinization, resulting in cell cycle arrest. Taken together, our data demonstrate the role of a novel heterochromatin-associated protein in transcriptional repression.
在真核生物中，高级染色质结构控制着包括 DNA 复制、转录和转录后基因调控在内的关键细胞过程。特定的染色质相互作用蛋白在维持染色质结构方面发挥着重要作用。我们已经鉴定出 BEND3，一种四重 BEN 结构域蛋白，在脊椎动物中高度保守。BEND3 在哺乳动物细胞的异染色质区域与 HP1 和 H3 三甲基化的 K9 共定位。使用体内基因座，我们已经能够证明，只有当基因座处于异染色质状态时，BEND3 才与该基因座结合，而在转录激活时则会分离。此外，将 BEND3 固定可抑制该基因座的转录，表明 BEND3 通过与组蛋白去乙酰化酶和转录抑制剂 Sall4 的相互作用参与转录抑制。我们进一步证明，BEND3 发生 SUMO 化，这种修饰对于其在转录抑制中的作用至关重要。最后，BEND3 的过表达导致过早的染色质浓缩和广泛的异染色质化，导致细胞周期停滞。综上所述，我们的数据表明了一种新型异染色质相关蛋白在转录抑制中的作用。
