Article ; Online: The C-terminal D/E-rich domain of MBD3 is a putative Z-DNA mimic that competes for Zα DNA-binding activity.
2018 Volume 46, Issue 22, Page(s) 11806–11821
Abstract: ... and revealed that Zα interacted with its C-terminal acidic region, an aspartate (D)/glutamate (E)-rich ... domain, with high affinity. The D/E-rich domain of MBD3 may act as a DNA mimic to compete with Z-DNA ... for binding to Zα. Dimerization of MBD3 via intermolecular interaction of the D/E-rich domain and its N ...
| Abstract | The Z-DNA binding domain (Zα), derived from the human RNA editing enzyme ADAR1, can induce and stabilize the Z-DNA conformation. However, the biological function of Zα/Z-DNA remains elusive. Herein, we sought to identify proteins associated with Zα to gain insight into the functional network of Zα/Z-DNA. By pull-down, biophysical and biochemical analyses, we identified a novel Zα-interacting protein, MBD3, and revealed that Zα interacted with its C-terminal acidic region, an aspartate (D)/glutamate (E)-rich domain, with high affinity. The D/E-rich domain of MBD3 may act as a DNA mimic to compete with Z-DNA for binding to Zα. Dimerization of MBD3 via intermolecular interaction of the D/E-rich domain and its N-terminal DNA binding domain, a methyl-CpG-binding domain (MBD), attenuated the high affinity interaction of Zα and the D/E-rich domain. By monitoring the conformation transition of DNA, we found that Zα could compete with the MBD domain for binding to the Z-DNA forming sequence, but not vice versa. Furthermore, co-immunoprecipitation experiments confirmed the interaction of MBD3 and ADAR1 in vivo. Our findings suggest that the interplay of Zα and MBD3 may regulate the transition of the DNA conformation between B- and Z-DNA and thereby modulate chromatin accessibility, resulting in alterations in gene expression. |
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| MeSH term(s) | Adenosine Deaminase/chemistry ; Binding Sites ; Biochemistry ; CpG Islands ; Cross-Linking Reagents/chemistry ; DNA/chemistry ; DNA, Z-Form/chemistry ; DNA-Binding Proteins/chemistry ; Gene Expression Profiling ; HEK293 Cells ; Humans ; Nucleic Acid Conformation ; Protein Binding ; Protein Domains ; Protein Multimerization ; RNA-Binding Proteins/chemistry |
| Chemical Substances | Cross-Linking Reagents ; DNA, Z-Form ; DNA-Binding Proteins ; MBD3 protein, human ; RNA-Binding Proteins ; DNA (9007-49-2) ; ADAR protein, human (EC 3.5.4.37) ; Adenosine Deaminase (EC 3.5.4.4) |
| Language | English |
| Publishing date | 2018-10-05 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 186809-3 |
| ISSN | 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048 |
| ISSN (online) | 1362-4962 ; 1362-4954 |
| ISSN | 0301-5610 ; 0305-1048 |
| DOI | 10.1093/nar/gky933 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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