Structural highlights
Disease
[CHD5_HUMAN] Defects in CHD5 may be a cause of the development of cancers from epithelial, neural and hematopoietic origin. CHD5 is one of the missing genes in the del(1p36), a deletion which is extremely common in this type of cancers. A decrease of its expression, results in increased susceptibility of cells to Ras-mediated transformation in vitro and in vivo (PubMed:17289567).[1]
Function
[CHD5_HUMAN] Chromatin-remodeling protein that binds DNA through histones and regulates gene transcription. May specifically recognize and bind trimethylated 'Lys-27' (H3K27me3) and non-methylated 'Lys-4' of histone H3. Plays a role in the development of the nervous system by activating the expression of genes promoting neuron terminal differentiation. In parallel, it may also positively regulate the trimethylation of histone H3 at 'Lys-27' thereby specifically repressing genes that promote the differentiation into non-neuronal cell lineages. Tumor suppressor, it regulates the expression of genes involved in cell proliferation and differentiation. Downstream activated genes may include CDKN2A that positively regulates the p53/TP53 pathway, which in turn, prevents cell proliferation. In spermatogenesis, it probably regulates histone hyperacetylation and the replacement of histones by transition proteins in chromatin, a crucial step in the condensation of spermatid chromatin and the production of functional spermatozoa.[2]
References
- ↑ Bagchi A, Papazoglu C, Wu Y, Capurso D, Brodt M, Francis D, Bredel M, Vogel H, Mills AA. CHD5 is a tumor suppressor at human 1p36. Cell. 2007 Feb 9;128(3):459-75. doi: 10.1016/j.cell.2006.11.052. PMID:17289567 doi:http://dx.doi.org/10.1016/j.cell.2006.11.052
- ↑ Egan CM, Nyman U, Skotte J, Streubel G, Turner S, O'Connell DJ, Rraklli V, Dolan MJ, Chadderton N, Hansen K, Farrar GJ, Helin K, Holmberg J, Bracken AP. CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression. Dev Cell. 2013 Aug 12;26(3):223-36. doi: 10.1016/j.devcel.2013.07.008. PMID:23948251 doi:http://dx.doi.org/10.1016/j.devcel.2013.07.008