Activity-dependent Neuroprotective Protein Constitutes a Novel Element in the SWI/SNF Chromatin Remodeling Complex
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Complete deficiency in activity-dependent neuroprotective protein (ADNP), a heterochromatin 1-binding protein, results in dramatic changes in gene expression, neural tube closure defects, and death at gestation day 9 in mice. To further understand the cellular roles played by ADNP, the HEK293 human embryonic kidney cell line that allows efficient transfection with recombinant DNA was used as a model for the identification of ADNP-interacting proteins. Recombinant green fluorescent protein (GFP)-ADNP was localized to cell nuclei. When nuclear extracts were subjected to immunoprecipitation with specific GFP antibodies followed by polyacrylamide gel electrophoresis, several minor protein bands were observed in addition to GFP-ADNP. In-gel protein digests followed by mass spectrometry identified BRG1, BAF250a, and BAF170, all components of the SWI/SNF (mating type switching/sucrose nonfermenting) chromatin remodeling complex, as proteins that co-immunoprecipitate with ADNP. These results were verified utilizing BRG1 antibodies. ADNP short hairpin RNA down-regulation resulted in microtubule reorganization and changes in cell morphology including reduction in cell process formation and cell number. These morphological changes are closely associated with the SWI/SNF complex multifunctionality. Taken together, the current study uncovers a molecular basis for the essential function of the ADNP gene and protein.
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ADNP is a transcription factor that participates in the SWI/SNF chromatin remodeling complex.
“a transcription factor involved in the SWI/SNF remodeling complex”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [36]
The C-terminal part of ADNP directly interacts with ARID1A, SMARCA4 and SMARCC2, three essential components of the BAF complexes.
“The C-terminal part of ADNP directly interacts with ARID1A, SMARCA4 and SMARCC2, three essential components of the BAF complexes, the functional eukaryotic equivalent of the SWI/SNF complex in yeast that is involved in the regulation of gene expression36.”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [36]
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- Authors
- Mandel, S., & Gozes, I.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Gozes, Illana
- ORCID
- Gozes, Illana
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 282
- Issue
- 47
- Pages
- 34448-34456
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2039291773
- Cited by
- 150
- References
- 27
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 14 · 2023: 10 · 2022: 8 · 2021: 5 · 2020: 17 · 2019: 10 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 8 · 2013: 3 · 2012: 3
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- ADNP, SWI/SNF complex, SMARCA4, ARID1A, BAF170, protein-protein interaction, microtubule reorganization, cell morphology, gene expression regulation
- MeSH terms
- Animals, Cell Line, Chromosomal Proteins, Non-Histone, DNA Helicases, DNA-Binding Proteins, Humans, Models, Biological, Nerve Tissue Proteins, Neural Tube Defects, Nuclear Proteins, Transcription Factors, Homeodomain Proteins, Gene Expression Regulation, Developmental, Chromatin Assembly and Disassembly, Mice, Neural Tube
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