Structural highlights
Disease
[SNF5_HUMAN] Neurofibromatosis type 3;Atypical teratoid rhabdoid tumor;Familial rhabdoid tumor;Familial multiple meningioma;Coffin-Siris syndrome. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
[SNF5_HUMAN] Core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Involved in activation of CSF1 promoter. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
SWI/SNF complexes use the energy of ATP hydrolysis to remodel chromatin. In mammals they play a central role in regulating gene expression during differentiation and proliferation. Mutations in SWI/SNF subunits are among the most frequent gene alterations in cancer. The INI1/hSNF5/SMARCB1 subunit is mutated in both malignant rhabdoid tumor, a highly aggressive childhood cancer, and schwannomatosis, a tumor-predisposing syndrome characterized by mostly benign tumors of the CNS. Here, we show that mutations in INI1 that cause schwannomatosis target a hitherto unidentified N-terminal winged helix DNA binding domain that is also present in the BAF45a/PHF10 subunit of the SWI/SNF complex. The domain is structurally related to the SKI/SNO/DAC domain, which is found in a number of metazoan chromatin-associated proteins.
The SWI/SNF Subunit INI1 Contains an N-Terminal Winged Helix DNA Binding Domain that Is a Target for Mutations in Schwannomatosis.,Allen MD, Freund SM, Zinzalla G, Bycroft M Structure. 2015 Jul 7;23(7):1344-9. doi: 10.1016/j.str.2015.04.021. Epub 2015 Jun, 11. PMID:26073604[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Phelan ML, Sif S, Narlikar GJ, Kingston RE. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol Cell. 1999 Feb;3(2):247-53. PMID:10078207
- ↑ Versteege I, Medjkane S, Rouillard D, Delattre O. A key role of the hSNF5/INI1 tumour suppressor in the control of the G1-S transition of the cell cycle. Oncogene. 2002 Sep 19;21(42):6403-12. PMID:12226744 doi:http://dx.doi.org/10.1038/sj.onc.1205841
- ↑ Oruetxebarria I, Venturini F, Kekarainen T, Houweling A, Zuijderduijn LM, Mohd-Sarip A, Vries RG, Hoeben RC, Verrijzer CP. P16INK4a is required for hSNF5 chromatin remodeler-induced cellular senescence in malignant rhabdoid tumor cells. J Biol Chem. 2004 Jan 30;279(5):3807-16. Epub 2003 Nov 6. PMID:14604992 doi:http://dx.doi.org/10.1074/jbc.M309333200
- ↑ Pan X, Song Z, Zhai L, Li X, Zeng X. Chromatin-remodeling factor INI1/hSNF5/BAF47 is involved in activation of the colony stimulating factor 1 promoter. Mol Cells. 2005 Oct 31;20(2):183-8. PMID:16267391
- ↑ Ulyanova NP, Schnitzler GR. Human SWI/SNF generates abundant, structurally altered dinucleosomes on polynucleosomal templates. Mol Cell Biol. 2005 Dec;25(24):11156-70. PMID:16314535 doi:http://dx.doi.org/10.1128/MCB.25.24.11156-11170.2005
- ↑ Morozov A, Yung E, Kalpana GV. Structure-function analysis of integrase interactor 1/hSNF5L1 reveals differential properties of two repeat motifs present in the highly conserved region. Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1120-5. PMID:9448295
- ↑ Allen MD, Freund SM, Zinzalla G, Bycroft M. The SWI/SNF Subunit INI1 Contains an N-Terminal Winged Helix DNA Binding Domain that Is a Target for Mutations in Schwannomatosis. Structure. 2015 Jul 7;23(7):1344-9. doi: 10.1016/j.str.2015.04.021. Epub 2015 Jun, 11. PMID:26073604 doi:http://dx.doi.org/10.1016/j.str.2015.04.021
