Zhang et al. (1998) reported the isolation of a protein complex that contains both histone deacetylation and ATP-dependent nucleosome remodeling activities. The complex contained the histone deacetylases HDAC1/2, histone-binding proteins, the dermatomyositis-specific autoantigen Mi2-beta, a polypeptide related to the metastasis-associated protein-1, and a novel polypeptide of 32 kD. Patients with dermatomyositis have a high rate of malignancy. The finding that Mi2-beta exists in a complex containing histone deacetylase and nucleosome remodeling activities suggests a role for chromatin reorganization in cancer metastasis.
NCBI Summary:
The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. Patients with dermatomyositis develop antibodies against the nuclear antigen chromodomain helicase DNA binding protein 4. The protein exists in a complex containing histone deacetylase and nucleosome remodeling activities, suggesting a role for chromatin reorganization in cancer metastasis.
General function
Oncogenesis, DNA binding
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Cellular localization
Nuclear
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Ovarian function
Antral follicle growth
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Expression regulated by
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Ovarian localization
Granulosa
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Metastasis-Associated Protein 3 (MTA3) Regulates G2/M Progression in Proliferating Mouse Granulosa Cells. Kwintkiewicz J et al. Metastasis associated protein 3 (MTA3) is a constituent of the Mi-2/nucleosome remodeling and deacetylase (NuRD) complex that regulates gene expression by altering chromatin structure and can facilitate cohesin loading onto DNA. The biological function of MTA3 within the NuRD complex is unknown. Here we show that MTA3 was expressed highly in granulosa cell nuclei of all ovarian follicle stages and at lower levels in corpora lutea. We tested the hypothesis that MTA3-NuRD complex function is required for granulosa cell proliferation. In the ovary, MTA3 interacted with NuRD proteins CHD4 and HDAC1 and the core cohesin complex protein RAD21. In cultured mouse primary granulosa cells, depletion of endogenous MTA3 using RNA interference slowed cell proliferation; this effect was rescued by co-expression of exogenous MTA3. Slowing of cell proliferation correlated with a significant decrease in cyclin B1 and cyclin B2 expression. Granulosa cell populations lacking MTA3 contained a significantly higher percentage of cells in G2/M phase and a lower percentage in S phase as compared to control cells. Furthermore, MTA3 depletion slowed entry into M phase as indicated by reduced phosphorylation of histone H3 at serine 10. These findings provide the first evidence that MTA3 interacts with NuRD and cohesin complex proteins in the ovary in vivo and regulates G2/M progression in proliferating granulosa cells.
Khattak S, e al reported the genetic characterization of Drosophila Mi-2 ATPase.
Mammalian Mi-2, an auto-antigen for dermatomyositis, is known to be an adenosine triphosphate (ATP)-dependent nucleosome remodelling factor. The Drosophila homologue of Mi-2 (dMi-2) gene is located at 76D5-6 on the left arm of the third chromosome and is transcribed into two alternate transcripts (dMi-2a and dMi-2b). Both transcripts are present at high levels in the ovary and during the first 8 h of embryogenesis when detected by Northern blot analysis. The localization of protein was nuclear, which is consistent with its proposed function as a component of the chromatin remodelling complex. Several lines of recessive mutants including mutations in dMi-2 were isolated and classified into four different complementation groups. Four alleles of dMi-2 mutants were further characterized in molecular nature; dMi-2(BL1) was found to have a mutation in the ATP-binding motif of the ATPase domain, dMi-2(BL7) in the core histidine of the first plant homeodomain zinc finger and dMi-2(BL12) in a conserved serine in the chromodomain. On the other hand, dMi-2(BL3) did not have any change in the coding region. The expression pattern of dMi-2 and the embryonic lethal phenotypes of mutants indicate that dMi-2 is essential for embryonic development in Drosophila melanagaster.