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A transcriptional coregulator, SPIN·DOC, attenuates the coactivator activity of Spindlin1.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2017 Dec 22; Vol. 292 (51), pp. 20808-20817. Date of Electronic Publication: 2017 Oct 23. - Publication Year :
- 2017
-
Abstract
- Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. SPIN1 harbors three Tudor domains, two of which engage the tail of histone H3 by reading the H3-Lys-4 trimethylation and H3-Arg-8 asymmetric dimethylation marks. To gain mechanistic insight into how SPIN1 functions as a transcriptional coactivator, here we purified its interacting proteins. We identified an uncharacterized protein (C11orf84), which we renamed SPIN1 docking protein (SPIN·DOC), that directly binds SPIN1 and strongly disrupts its histone methylation reading ability, causing it to disassociate from chromatin. The Spindlin family of coactivators has five related members (SPIN1, 2A, 2B, 3, and 4), and we found that all of them bind SPIN·DOC. It has been reported previously that SPIN1 regulates gene expression in the Wnt signaling pathway by directly interacting with transcription factor 4 (TCF4). We observed here that SPIN·DOC associates with TCF4 in a SPIN1-dependent manner and dampens SPIN1 coactivator activity in TOPflash reporter assays. Furthermore, knockdown and overexpression experiments indicated that SPIN·DOC represses the expression of a number of SPIN1-regulated genes, including those encoding ribosomal RNA and the cytokine IL1B. In conclusion, we have identified SPIN·DOC as a transcriptional repressor that binds SPIN1 and masks its ability to engage the H3-Lys-4 trimethylation activation mark.<br /> (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Carrier Proteins chemistry
Carrier Proteins genetics
Cell Cycle Proteins chemistry
Cell Cycle Proteins genetics
Chromatin metabolism
Co-Repressor Proteins chemistry
Co-Repressor Proteins genetics
Gene Expression Regulation
Gene Knockdown Techniques
HEK293 Cells
Histones metabolism
Humans
Methylation
Microtubule-Associated Proteins chemistry
Microtubule-Associated Proteins genetics
Phosphoproteins chemistry
Phosphoproteins genetics
Protein Interaction Domains and Motifs
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Trans-Activators chemistry
Trans-Activators genetics
Transcription Factor 4 metabolism
Wnt Signaling Pathway
Carrier Proteins metabolism
Cell Cycle Proteins metabolism
Co-Repressor Proteins metabolism
Microtubule-Associated Proteins metabolism
Phosphoproteins metabolism
Trans-Activators metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 292
- Issue :
- 51
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29061846
- Full Text :
- https://doi.org/10.1074/jbc.M117.814913