Alternative titles; symbols
HGNC Approved Gene Symbol: MTA2
Cytogenetic location: 11q12.3 Genomic coordinates (GRCh38) : 11:62,593,214-62,601,865 (from NCBI)
By sequence analysis of randomly selected human adult heart cDNA clones, Futamura et al. (1999) identified MTA1-like-1 (MTA1L1), a gene that shows significant sequence similarity to MTA1 (603526). The full-length MTA1L1 cDNA sequence encodes a deduced 668-amino acid protein containing putative zinc finger and leucine zipper motifs, as well as several possible phosphorylation sites. The MTA1L1 and MTA1 proteins are 59.6% identical. Northern blot analysis detected a 3.0-kb MTA1L1 transcript in all human adult tissues examined.
The p53 tumor suppressor (191170) is a transcriptional factor whose activity is modulated by protein stability and posttranslational modifications including acetylation. Luo et al. (2000) showed that deacetylation of p53 is mediated by a histone deacetylase-1 (HDAC1; 601241)-containing complex. They also purified a p53 target protein, which they named PID, in the deacetylase complexes. PID is identical to MTA1L1, also called MTA2, which had been identified as a component of the nucleosome remodeling and histone deacetylation (NURD) complex. The authors found that MTA1L1 specifically interacts with p53 both in vitro and in vivo, and its expression reduces significantly the steady-state levels of acetylated p53. MTA1L1 expression strongly represses p53-dependent transcriptional activation, and, notably, it modulates p53-mediated cell growth arrest and apoptosis. Luo et al. (2000) concluded that their results show that deacetylation and functional interactions between the MTA1L1-associated NURD complex may represent an important pathway to regulate p53 function.
Zhang et al. (1999) showed that MTA2 and the 32-kD MBD3 (603573) protein are subunits of the NURD complex. Immunoprecipitation analysis showed that MBD3 interacts with HDAC1, RBBP4 (602923), and RBBP7 (300825), but not with MI2 (CHD4; 603277), suggesting that MBD3 is embedded within the NURD complex. The authors found that MTA2 directs the assembly of an active histone deacetylase complex and that the association of MTA2 with the complex requires MBD3. Gel mobility shift analysis determined that both NURD and MBD3 are unable to bind to methylated DNA in the absence of MBD2 (603547). Zhang et al. (1999) proposed that NURD is involved in the transcriptional repression of methylated DNA. Wade et al. (1999) also identified MTA1, MTA1L, and MBD3 as components of the NURD complex, which they referred to as the MI2 complex.
Futamura et al. (1999) determined that the MTA1L1 gene contains 18 exons and spans approximately 8.1 kb.
By FISH, Futamura et al. (1999) mapped the MTA1L1 gene to 11q12-q13.1. Using FISH, Cui et al. (2001) mapped the mouse Mta1l1 gene to chromosome 19B.
Cui, Q., Matsusue, K., Toh, Y., Kono, A., Takiguchi, S. Assignment of the metastasis-associated gene (Mta1) to mouse chromosome band 12F and the metastasis-associated gene 2 (Mta2) to mouse chromosome band 19B by fluorescence in situ hybridization. Cytogenet. Cell Genet. 94: 246-247, 2001. [PubMed: 11856890] [Full Text: https://doi.org/10.1159/000048825]
Futamura, M., Nishimori, H., Shiratsuchi, T., Saji, S., Nakamura, Y., Tokino, T. Molecular cloning, mapping, and characterization of a novel human gene, MTA1-L1, showing homology to a metastasis-associated gene, MTA1. J. Hum. Genet. 44: 52-56, 1999. [PubMed: 9929979] [Full Text: https://doi.org/10.1007/s100380050107]
Luo, J., Su, F., Chen, D., Shiloh, A., Gu, W. Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408: 377-381, 2000. [PubMed: 11099047] [Full Text: https://doi.org/10.1038/35042612]
Wade, P. A., Gegonne, A., Jones, P. L., Ballestar, E., Aubry, F., Wolffe, A. P. Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nature Genet. 23: 62-66, 1999. [PubMed: 10471500] [Full Text: https://doi.org/10.1038/12664]
Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., Reinberg, D. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 13: 1924-1935, 1999. [PubMed: 10444591] [Full Text: https://doi.org/10.1101/gad.13.15.1924]