scholarly journals Oligomerization and Binding of the Dnmt3a DNA Methyltransferase to Parallel DNA Molecules

2011 ◽  
Vol 286 (27) ◽  
pp. 24200-24207 ◽  
Author(s):  
Renata Z. Jurkowska ◽  
Arumugam Rajavelu ◽  
Nils Anspach ◽  
Claus Urbanke ◽  
Gytis Jankevicius ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Protein Interaction ◽  
Dna Methyltransferase ◽  
Structural Studies ◽  
Dna Molecules ◽  
Protein Protein Interaction ◽  
Dna Molecule ◽  
Dna Binding Site ◽  
In Cells

Structural studies showed that Dnmt3a has two interfaces for protein-protein interaction in the heterotetrameric Dnmt3a/3L C-terminal domain complex: the RD interface (mediating the Dnmt3a-3a contact) and the FF interface (mediating the Dnmt3a-3L contact). Here, we demonstrate that Dnmt3a-C forms dimers via the FF interface as well, which further oligomerize via their RD interfaces. Each RD interface of the Dnmt3a-C oligomer creates an independent DNA binding site, which allows for binding of separate DNA molecules oriented in parallel. Because Dnmt3L does not have an RD interface, it prevents Dnmt3a oligomerization and binding of more than one DNA molecule. Both interfaces of Dnmt3a are necessary for the heterochromatic localization of the enzyme in cells. Overexpression of Dnmt3L in cells leads to the release of Dnmt3a from heterochromatic regions, which may increase its activity for methylation of euchromatic targets like the differentially methylated regions involved in imprinting.

scholarly journals Determinants for DNA-binding site recognition by the glucocorticoid receptor.

1992 ◽  
Vol 267 (35) ◽  
pp. 24941-24947
Author(s):  
J Zilliacus ◽  
A.P. Wright ◽  
U Norinder ◽  
J.A. Gustafsson ◽  
J Carlstedt-Duke
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Binding Site ◽  
Dna Binding Site ◽  
Site Recognition

scholarly journals Hesx1 homeodomain protein represses transcription as a monomer and antagonises transactivation of specific sites as a homodimer

2002 ◽  
Vol 28 (3) ◽  
pp. 193-205 ◽  
Author(s):  
J Quirk ◽  
P Brown
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Binding Site ◽  
Anterior Pituitary ◽  
Homeodomain Protein ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Differentiation Markers ◽  
Proximal Half ◽  
Dna Binding Site

The homeobox repressor Hesx1, expressed throughout Rathke's pouch and required for normal pituitary development, has been implicated in anterior pituitary pathogenesis in man. Prolonged expression of Hesx1 delays the appearance of anterior pituitary terminal differentiation markers in mice, particularly the gonadotroph hormones. We tested if Hesx1 could modulate gonadotrophin gene expression directly, and found that Hesx1 repressed both common alpha subunit (alpha GSU) and luteinising hormone beta-subunit (LH beta) gene promoters. Repression mapped to the Pitx1 homeodomain protein transactivation site in the proximal alpha GSU promoter, but did not map to the equivalent site on LH beta. Hesx1 repression of the alpha GSU Pitx1 site was overridden by co-transfection of Pitx1. In contrast, Hesx1 antagonised Pitx1 transactivation of LH beta in a dose-dependent manner. This was due to monomeric binding of Hesx1 on alpha GSU and homodimerisation on LH beta. The homodimerisation site comprises the Pitx1 DNA binding site and a proximal binding site, and mutation of either inhibited homodimer formation. Conversion of the LH beta Pitx1 DNA binding site to an alpha GSU-type did not promote homodimer formation, arguing that Hesx1 has pronounced site selectivity. Furthermore, mutation of the proximal half of the homodimerisation site blocked Hesx1 antagonisation of Pitx1 transactivation. We conclude that Hesx1 monomers repress gene expression, and homodimers block specific transactivation sites.

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