增殖细胞核抗原是将 SMCX/KMD5C 组蛋白去甲基酶加载到染色质上所必需的。

Proliferating cell nuclear antigen is required for loading of the SMCX/KMD5C histone demethylase onto chromatin.

机构信息

Division of Infectious Diseases - Center for Human Virology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.

出版信息

Epigenetics Chromatin. 2011 Oct 13;4(1):18. doi: 10.1186/1756-8935-4-18.

BACKGROUND

Histone methylation is regulated by a large number of histone methyltransferases and demethylases. The recently discovered SMCX/KMD5C demethylase has been shown to remove methyl residues from lysine 4 of histone H3 (H3K4), and constitutes an important component of the regulatory element-1-silencing transcription factor (REST) protein complex. However, little is known about the cellular mechanisms that control SMCX activity and intracellular trafficking.

RESULTS

In this study, we found that small interfering RNA-mediated knockdown of proliferating cell nuclear antigen (PCNA) resulted in the reduction of the chromatin-bound SMCX fraction. We identified a PCNA-interaction protein motif (PIP box) in the SMCX protein. Using site-directed mutagenesis, we found that the amino acids of the SMCX PIP box are involved in the association of SMCX with PCNA and its interaction with chromatin.

CONCLUSIONS

Our data indicate that the intracellular trafficking of SMCX is controlled by its association with PCNA.

背景

组蛋白甲基化受大量组蛋白甲基转移酶和去甲基酶调控。最近发现的 SMCX/KMD5C 去甲基酶已被证实能从组蛋白 H3 的赖氨酸 4（H3K4）上去除甲基残基，它是调控元件-1 沉默转录因子（REST）蛋白复合物的重要组成部分。然而，目前对于控制 SMCX 活性和细胞内运输的细胞机制还知之甚少。

结果

在这项研究中，我们发现，增殖细胞核抗原（PCNA）的小干扰 RNA 介导的敲低导致染色质结合的 SMCX 分数减少。我们在 SMCX 蛋白中鉴定出一个 PCNA 相互作用蛋白基序（PIP 盒）。通过定点突变，我们发现 SMCX PIP 盒的氨基酸参与了 SMCX 与 PCNA 的结合及其与染色质的相互作用。