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chromatin-modifying proteins

Thursday 20 November 2003

Mammalian cells contain several chromatin-remodeling complexes associated with the Brm and Brg1 helicase-like proteins. These complexes likely represent the functional homologs of the SWI/SNF and RSC complexes found in Saccharomyces cerevisiae.

The mammalian chromatin-remodeling complexes are involved in both activation and repression of a variety of genes. Several lines of evidence also indicate that they play a specific role in the regulation of cell growth.

The action of multi-subunit complexes that are able to overcome the repressive effects of chromatin is an important step in the regulation of eukaryotic gene expression.

Identification of complexes that modify the structure of chromatin to help factors access the underlying DNA has enhanced our understanding of how some genes are controlled.

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) represent one group of complexes that regulate the level of acetylation on the N-terminal tails of core histone proteins.

The SWI/SNF complex is the prototype of a second group of complexes, which use the energy of ATP-hydrolysis to alter histone-DNA contacts, leading to changes in chromatin conformation.

Members

- Brm is down-regulated by ras signaling and its forced re-expression suppresses transformation by this oncogene.
- Brg1 gene is silenced or mutated in several tumors cell lines and a Brg1-associated complex was recently found to co-purify with BRCA1, involved in breast and ovarian cancers.
- SWI/SNF (INI1 - SNF5) is a subunit common to all mammalian SWI/SNF complexes, is inactivated in malignant rhabdoid tumor, a very aggressive form of pediatric cancer.

See also

- chromatin-modifying complexes

References

- Di Croce L. Chromatin modifying activity of leukaemia associated fusion proteins. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R77-84. PMID: 15809276

- Gibbons RJ. Histone modifying and chromatin remodelling enzymes in cancer and dysplastic syndromes. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R85-92. PMID: 15809277

- Gregory RI, Shiekhattar R. Chromatin modifiers and carcinogenesis. Trends Cell Biol. 2004 Dec;14(12):695-702. PMID: 15564046

- Muchardt C, Yaniv M. When the SWI/SNF complex remodels...the cell cycle. Oncogene. 2001 May 28;20(24):3067-75. PMID: 11420722

- Muchardt C, Yaniv M. The mammalian SWI/SNF complex and the control of cell growth. Semin Cell Dev Biol. 1999 Apr;10(2):189-95. PMID: 10441072