MBD2 contributes to developmental silencing of the human ε-globin gene

p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex.

Nucleosome remodeling complexes comprise several large families of chromatin modifiers that integrate multiple epigenetic control signals to play key roles in cell type-specific transcription regulation. We previously isolated a methyl-binding domain protein 2 (MBD2)-containing nucleosome remodeling and deacetylation (NuRD) complex from primary erythroid cells and showed that MBD2 contributes t...

g-Globin Promoter Prevents Silencing of a Linked Human b-Globin Gene in Transgenic Mice

Developmental specificity of recruitment of TBP to the TATA box of the human -globin gene

It is unclear whether the core promoter is involved in developmental regulation. To address this question, we mutated the TATA box of the human -globin gene, produced transgenic mice, and examined the effect of the mutation during the course of mouse development. In our test system, the -globin gene is expressed at similar levels in the embryonic and adult erythroid cells. The TATA box mutation...

Identification of a PRMT5-dependent repressor complex linked to silencing of human fetal globin gene expression.

Defining the molecular mechanisms underpinning fetal (gamma) globin gene silencing may provide strategies for reactivation of gamma-gene expression, a major therapeutic objective in patients with beta-thalassemia and sickle cell disease (SCD). We have previously demonstrated that symmetric methylation of histone H4 Arginine 3 (H4R3me2s) by the protein arginine methyltransferase PRMT5 is require...

Mbd2 contributes to DNA methylation-directed repression of the Xist gene.

Transcription of the Xist gene triggers X chromosome inactivation in cis and is therefore silenced on the X chromosome that remains active. DNA methylation contributes to this silencing, but the mechanism is unknown. As methylated DNA binding proteins (MBPs) are potential mediators of gene silencing by DNA methylation, we asked whether MBP-deficient cell lines could maintain Xist repression. Th...