Abstract
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 β-globin gene cluster, it is unclear that how these MAR elements are involved in regulating β-globin genes expression. Here, we report the identification of a new MAR element at the LCR(locus control region) of human β-globin gene cluster and the detection of the inter-MAR association within the β-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 β-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 α-like globin genes and β-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.
Highlights
Many studies have shown that a transcriptionally active structure can be formed when genes express actively
By observing the positions of the Matrix attachment regions (MARs) elements and the interactions among them, we showed the existence of a inter-MAR association structure mediated by SATB1 and the contribution of this structure to b-globin genes expression
We observed the maintaining of the binding of SATB1 to these MARs, that is possibly important for inter-MAR association and the reactivation of genes transcription in cell cycle
Summary
Many studies have shown that a transcriptionally active structure can be formed when genes express actively. Several assays including 3C [1], ChIP-3C/Loop assay [2,3], DamID [4] and other approaches have been applied to show that the chromatin looping events can bring distal regulatory elements and related gene promoters into close proximity and provide such a transcriptionally active structure. MARs are originally identified as genomic DNA fragments that remain tightly associated with high saltextracted and DNase I–digested nuclei, and have been postulated to be localized at the base of chromatin loops. The MARs help to form the chromatin loops by attaching to the nuclear matrix. SATB1, which has been characterized as a MAR-binding protein, can bind to the BUR sequences and regulates higher order chromatin loop structures in T-cell[19,20,21]. Kumar et al showed that SATB1 can recruit a regulatory complex that manages transcription by orchestrating dynamic chromatin-loop architecture in MHC class I locus [21]
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