A Conserved 12-Amino Acid Motif in Sall1 Recruits the Nucleosome Remodeling and Deacetylase Corepressor Complex
Open accessAbstract
Sall1 is a multi-zinc finger transcription factor that represses gene expression and regulates organogenesis. In this report, we further characterize the domain of Sall1 necessary for repression. We show that endogenous Sall1 binds to the nucleosome remodeling and deacetylase corepressor complex (NuRD) and confirm the functionality of the Sall1-associating macromolecular complex by showing that the complex possesses HDAC activity. NuRD is involved in global transcriptional repression and regulation of specific developmental processes. The mechanism by which sequence-specific DNA-binding proteins associate with NuRD is not well understood. We have identified a highly conserved 12-amino acid motif in the transcription factor Sall1 that is sufficient for the recruitment of NuRD. Single amino acid substitutions defined the critical amino acid peptide motif as RRKQXK-PXXF. This motif probably exhibits a more general role in regulating gene expression, since other proteins containing this domain, including all Sall family members and an unrelated zinc finger protein Ebfaz, mediate transcriptional repression and associate with NuRD. These results also have important implications for the pathogenesis of Townes-Brocks, a syndrome caused by SALL1 mutations.
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The extreme N terminus of SALL4 interacts specifically with the NuRD co-repressor complex and can account for transcriptional repression caused by SALL4 recruitment to reporter genes.
“The extreme N terminus interacts specifically with the nucleosome remodeling and deacetylase (NuRD) co-repressor complex and can account for the transcriptional repression caused by SALL4 recruitment to reporter genes (Lauberth and Rauchman, 2006; Lu et al., 2009).”
From SALL4 controls cell fate in response to DNA base composition (2021) · cites this paper as Lauberth and Rauchman, 2006
The N-terminal NuRD binding motif is comparatively depleted of population missense mutations (VdVp = 0.22).
“Three regions were observed to be comparatively depleted of population missense mutations: the N-terminal NuRD binding motif (Lauberth & Rauchman, 2006) (VdVp = 0.22); a glutamine-rich (Q-rich) sequence that has been reported to participate in SALL protein homo- and heterodimer formation (VdVp = 0.50) (Sweetman et al, 2003); and ZFC4, which is essential for SALL4 function in mice (VdVp = 0.47) (P”
From Structure of SALL4 zinc finger domain reveals link between AT-rich DNA binding and Okihiro syndrome (2023) · cites this paper as Lauberth & Rauchman, 2006
SALL proteins are C2H2 zinc-finger transcription factors important for embryogenesis.
“Spalt-like (SALL) proteins are C2H2 zinc-finger transcription factors important for embryogenesis”
From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [3]
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“In this study, we report that SALL4, a protein containing the same conserved 12 amino acid motif [22,24,27], associates with the NuRD complex and functions as a strong transcription repressor.”
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Do short, frequent DNA sequence motifs mould the epigenome
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Structure of SALL4 zinc finger domain reveals link between AT-rich DNA binding and Okihiro syndrome
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“Three regions were observed to be comparatively depleted of population missense mutations: the N-terminal NuRD binding motif (Lauberth & Rauchman, 2006) (VdVp = 0.22); a glutamine-rich (Q-rich) sequence that has been reported to participate in SALL protein homo-and heterodimer formation (VdVp =…”
InfluentialZhang, T., Wang, Y.-F., Montoya, A., Patrascan, I., Nebioglu, N., Pallikonda, H. A., Georgieva, R., King, J. W. D., Kramer, H. B., Shliaha, P. V., et al. (2025) · Blood · doi:10.1182/blood.2024024787 · Cited by 14 · see citing works
Tetramerisation governs SALL transcription factor function in development and disease
Giuliani, S., Chhatbar, K., Wear, M., Guy, J., Mathieson, T., Burdett, H., George, L., Alston, G., Spanos, C., McHugh, T., et al. (2025) · bioRxiv · doi:10.1101/2025.10.27.684836
- Authors
- Lauberth, S. M., & Rauchman, M.
- Affiliations
- St. Louis VA Medical Center (US)
- Corresponding author
- Rauchman, Michael
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 281
- Issue
- 33
- Pages
- 23922-23931
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1968962291
- Cited by
- 140
- References
- 5
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 12 · 2023: 3 · 2022: 3 · 2021: 12 · 2020: 7 · 2019: 4 · 2018: 12 · 2017: 8 · 2016: 6 · 2015: 6 · 2014: 10 · 2013: 3 · 2012: 3
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R35GM128900)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067222, DK067222)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- SALL1, NuRD complex, transcriptional repression, zinc finger transcription factor, histone deacetylase activity, protein-protein interaction, Townes-Brocks syndrome, gene expression regulation
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, DNA-Binding Proteins, Histone Deacetylases, Humans, Molecular Sequence Data, Peptide Mapping, Protein Binding, Repressor Proteins, Transcription Factors, Zinc Fingers, Conserved Sequence, Sequence Homology, Amino Acid, Amino Acid Motifs, Cell Line, Tumor, Mice, Mi-2 Nucleosome Remodeling and Deacetylase Complex
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