Abstract
Matrix attachment region (MAR)-binding protein (MARBP) has profound influence on gene transcriptional control by tethering genes to the nuclear scaffold. MARBP SATB2 is recently known as a versatile regulator functioning in the differentiation of multiple cell types including embryonic stem cells, osteoblasts and immunocytes. Roles of SATB2 in erythroid cells and its working mechanism in orchestrating target gene expression are largely unexplored. We show here that SATB2 is expressed in erythroid cells and activates γ-globin genes by binding to MARs in their promoters and recruiting histone acetylase PCAF. Further analysis in higher-order chromatin structure shows that SATB2 affects physical proximity of human (G)γ- and (A)γ-globin promoters via self-association. We also found that SATB2 interacts with SATB1, which specifically activates ε-globin gene expression. Our results establish SATB2 as a novel γ-globin gene regulator and provide a glimpse of the differential and cooperative roles of SATB family proteins in modulating clustered genes transcription and mediating higher-order chromatin structures.
Highlights
Matrix attachment region-binding proteins regulate gene expression through anchoring chromatin loops to nuclear scaffold
Each error bar represents a standard deviation calculated from experiments performed in triplicate
We show here that the Matrix attachment region (MAR)-binding protein SATB2, a homolog of SATB1, transcriptionally activates the G␥ and A␥-globin genes in erythroid cells by directly binding to MAR elements at their promoters, recruiting co-activator PCAF and modulating the spatial proximity between the two ␥-globin promoters
Summary
Matrix attachment region-binding proteins regulate gene expression through anchoring chromatin loops to nuclear scaffold. Our results establish SATB2 as a novel ␥-globin gene regulator and provide a glimpse of the differential and cooperative roles of SATB family proteins in modulating clustered genes transcription and mediating higher-order chromatin structures. Our previous study showed that SATB1 tethers ⑀-globin gene to the nuclear matrix and identified SATB1-mediated inter-MAR association in the -globin gene locus accompanying the expression of ⑀-globin gene [14, 15], modulation of SATB1 acetylation by SIRT1 facilitates MARHS2-MAR⑀ association and promotes ⑀-globin expression [16] These studies on SATB1 suggest a potential role of MARbased higher-order chromatin structures fundamental to the organization of ACH. The present work, together with our previously identified SATB1-centered inter-MAR association, hints potential differentiation and cooperation of SATB family proteins in regulating the expression and higher-order chromatin structure organization of a gene cluster
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