Inter-MAR association contributes to transcriptionally active looping events in human beta-globin gene cluster.
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.
Wang
Li
L
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.
Di
Li-Jun
LJ
Lv
Xiang
X
Zheng
Wei
W
Xue
Zheng
Z
Guo
Zhi-Chen
ZC
Liu
De-Pei
DP
Liang
Chi-Chuan
CC
D000107:Acetylation; D002453:Cell Cycle; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000502:physiology; D045170:Matrix Attachment Regions; D005810:Multigene Family; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics*
D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human; D055544:beta-Globins