The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers.
The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers.
复制标题
DOI：
10.1016/j.celrep.2013.12.021
复制
发表时间：
2014-01-30
期刊：
影响因子：
8.8
通讯作者：
Kutateladze TG
中科院分区：
文献类型：
--
作者：
Klein BJ;Piao L;Xi Y;Rincon-Arano H;Rothbart SB;Peng D;Wen H;Larson C;Zhang X;Zheng X;Cortazar MA;Peña PV;Mangan A;Bentley DL;Strahl BD;Groudine M;Li W;Shi X;Kutateladze TG
组蛋白赖氨酸脱甲基酶KDM5B调节基因转录和细胞分化。它包含三个博士学位手指，其生物学作用仍然难以捉摸。在这里，我们表明KDM5B的第一个PHD1手指结合未修饰的组蛋白H3，而第三个PHD3指的手指则偏爱三甲基化标记H3K4Me3。 RNA-seq分析表明KDM5B充当一组基因的转录阻遏物。生化分析表明，KDM5B与核小体重塑和脱乙酰基酶（NURD）复合物的成分相关，并且可以在基因抑制中与HDAC1合作。与雌激素受体阳性乳腺癌相比，KDM5B在三阴性乳腺癌中被下调。 MDA-MB 231乳腺癌细胞中KDM5B的过表达抑制细胞迁移和侵袭能力，而PHD1-H3K4ME0相互作用对于抑制迁移至关重要。这些发现突出了KDM5B在三阴性乳腺癌细胞中的肿瘤抑制功能，并提出了KDM5B介导的转录调控的新型多价机制。
The histone lysine demethylase KDM5B regulates gene transcription and cell differentiation. It contains three PHD fingers, the biological roles of which remain elusive. Here, we show that the first PHD1 finger of KDM5B binds unmodified histone H3, whereas the third PHD3 finger prefers the trimethylated mark, H3K4me3. RNA-seq analysis indicates that KDM5B functions as a transcriptional repressor for a set of genes. Biochemical analysis reveals that KDM5B associates with components of the nucleosome remodeling and deacetylase (NuRD) complex and may cooperate with HDAC1 in gene repression. Compared with the estrogen receptor positive breast cancers, KDM5B is downregulated in the triple-negative breast cancer. Overexpression of KDM5B in the MDA-MB 231 breast cancer cells suppresses cell migration and invasion ability, and the PHD1-H3K4me0 interaction is important for inhibition of migration. These findings highlight tumor-suppressive functions of KDM5B in triple-negative breast cancer cells and suggest a novel multivalent mechanism for KDM5B-mediated transcriptional regulation.
登录
查看更多内容
影响因子：
64.5
作者：
Roesch A;Fukunaga-Kalabis M;Schmidt EC;Zabierowski SE;Brafford PA;Vultur A;Basu D;Gimotty P;Vogt T;Herlyn M
通讯作者：
Herlyn M
影响因子：
37.3
作者：
Hayami S;Yoshimatsu M;Veerakumarasivam A;Unoki M;Iwai Y;Tsunoda T;Field HI;Kelly JD;Neal DE;Yamaue H;Ponder BA;Nakamura Y;Hamamoto R
通讯作者：
Hamamoto R
影响因子：
64.5
作者：
Klose, Robert J.;Yan, Qin;Kaelin, William G., Jr.
通讯作者：
Kaelin, William G., Jr.
影响因子：
16.8
作者：
Lee, Nara;Zhang, Junyu;Zhang, Yi
通讯作者：
Zhang, Yi
影响因子：
3.7
作者：
Nijwening JH;Geutjes EJ;Bernards R;Beijersbergen RL
通讯作者：
Beijersbergen RL