Wang Li, Di Li-Jun, Lv Xiang, Zheng Wei, Xue Zheng, Guo Zhi-Chen, Liu De-Pei, Liang Chi-Chuan
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
PLoS One. 2009;4(2):e4629. doi: 10.1371/journal.pone.0004629. Epub 2009 Feb 27.
Matrix attachment regions (MARs) are important in chromatin organization and gene regulation. Although it is known that there are a number of MAR elements in the beta-globin gene cluster, it is unclear that how these MAR elements are involved in regulating beta-globin genes expression. Here, we report the identification of a new MAR element at the LCR (locus control region) of human beta-globin gene cluster and the detection of the inter-MAR association within the beta-globin gene cluster. Also, we demonstrate that SATB1, a protein factor that has been implicated in the formation of network like higher order chromatin structures at some gene loci, takes part in beta-globin specific inter-MAR association through binding the specific MARs. Knocking down of SATB1 obviously reduces the binding of SATB1 to the MARs and diminishes the frequency of the inter-MAR association. As a result, the ACH establishment and the alpha-like globin genes and beta-like globin genes expressions are affected either. In summary, our results suggest that SATB1 is a regulatory factor of hemoglobin genes, especially the early differentiation genes at least through affecting the higher order chromatin structure.
基质附着区域（MARs）在染色质组织和基因调控中起着重要作用。尽管已知在β-珠蛋白基因簇中有许多MAR元件，但尚不清楚这些MAR元件如何参与调控β-珠蛋白基因的表达。在此，我们报告了在人β-珠蛋白基因簇的LCR（基因座控制区）中鉴定出一个新的MAR元件，并检测到β-珠蛋白基因簇内MAR之间的相互作用。此外，我们证明了SATB1，一种在某些基因位点参与形成网络状高阶染色质结构的蛋白质因子，通过结合特定的MAR参与β-珠蛋白特异性的MAR之间的相互作用。敲低SATB1明显降低了SATB1与MAR的结合，并减少了MAR之间相互作用的频率。结果，ACH的建立以及α-样珠蛋白基因和β-样珠蛋白基因的表达均受到影响。总之，我们的结果表明SATB1是血红蛋白基因的调控因子，尤其是至少通过影响高阶染色质结构来调控早期分化基因。
