|
NuRD
In the field of molecular biology, the Mi-2/NuRD (Nucleosome Remodeling Deacetylase) complex, is a group of associated proteins with both ATP-dependent chromatin remodeling and histone deacetylase activities. , Mi-2/NuRD was the only known protein complex that couples chromatin remodeling ATPase and chromatin deacetylation enzymatic functions. The NuRD complex contains seven subunits: the histone deacetylase core proteins HDAC1 and HDAC2, the histone-binding proteins RbAp46 and RbAp48, the metastasis-associated proteins MTA1 (or MTA2 / MTA3), the methyl-CpG-binding domain protein MBD3 (or MBD2) and the chromodomain-helicase-DNA-binding protein CHD3 (aka Mi-2alpha) or CHD4 (aka Mi-2beta). The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs. Depletion of Mbd3, on the other hand, improves rep ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MBD3
Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the ''MBD3'' gene. Function DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). However, unlike the other family members, MBD3 is not capable of binding to methylated DNA but instead binds to hydroxymethylated DNA. The predicted MBD3 protein shares 71% and 94% identity with MBD2 (isoform 1) and mouse Mbd3. MBD3 is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. MBD3 mediates the association of metastasis-associated protein 2 (MTA2) with the core histone deacetylase complex. MBD3 also contains the coiled‐coil domain common to all three MBD3 isoforms. The coiled‐coil domain, but not the MBD domain, helps to ma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chromatin Remodeling
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MBD2
Methyl-CpG-binding domain protein 2 is a protein that in humans is encoded by the ''MBD2'' gene. Function DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG-binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1, and MBD2 can also repress transcription from methylated gene promoters. The protein encoded by these genes may function as a mediator of the biological consequences of the methylation signal. It is also reported that MBD2 and MBD3 recruit the NuRD complex to regions of DNA depending on their selective binding of methylated CpG sites. Therefore, MBD2/NuRD and MBD3/NuRD define two distinct protein complexes with different biochemical and functional properties. Interactions Methyl-CpG-bin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MTA3
Metastasis-associated protein MTA3 is a protein that in humans is encoded by the ''MTA3'' gene. MTA3 protein localizes in the nucleus as well as in other cellular compartments MTA3 is a component of the nucleosome remodeling and deacetylate (NuRD) complex and participates in gene expression. The expression pattern of MTA3 is opposite to that of MTA1 and MTA2 during mammary gland tumorigenesis. However, MTA3 is also overexpressed in a variety of human cancers. Discovery Mouse Mta3 was initially identified as a partial cDNA with open reading frames in screening of a mouse keratinocyte cDNA library with a human MTA1 partial fragment by My G. Mahoney's research team. The full length Mta3 cDNA was cloned through 5'-RACE Rapid amplification of cDNA ends (RACE) is a technique used in molecular biology to obtain the full length sequence of an RNA transcript found within a cell. RACE results in the production of a cDNA copy of the RNA sequence of interest, produced th ... methodology u ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MTA1
Metastasis-associated protein MTA1 is a protein that in humans is encoded by the ''MTA1'' gene. MTA1 is the founding member of the MTA family of genes. MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nuclear compartments. MTA1 is a component of several chromatin remodeling complexes including the nucleosome remodeling and deacetylation complex (NuRD). MTA1 regulates gene expression by functioning as a coregulator to integrate DNA-interacting factors to gene activity. MTA1 participates in physiological functions in the normal and cancer cells. MTA1 is one of the most upregulated proteins in human cancer and associates with cancer progression, aggressive phenotypes, and poor prognosis of cancer patients. Discovery ''MTA1'' was first cloned by Toh, Pencil and Nicholson in 1994 as a differentially expressed gene in a highly metastatic rat breast cancer cell line. The role in MTA1 in chromatin remodeling was deduced due to the presence of MT ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC1
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene. Function Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family and is a component of the histone deacetylase complex. It also interacts with retinoblastoma tumor-suppressor protein and this complex is a key element in the control of cell proliferation and differentiation. Together with metastasis-associated protein-2 MTA2, it deacetylates p53 and modulates its effect on cell growth and apoptosis. Model organisms Model organisms have been used in the study of HDAC1 function. A conditional knockout mouse line, called ''Hdac1tm1a(EUCOMM)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to inte ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CHD3
Chromodomain-helicase-DNA-binding protein 3 is an enzyme that in humans is encoded by the ''CHD3'' gene. Function This gene encodes a member of the CHD family of proteins which are characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. This protein is one of the components of a histone deacetylase complex referred to as the Mi-2/NuRD complex which participates in the remodeling of chromatin by deacetylating histones. Chromatin remodeling is essential for many processes including transcription. Autoantibodies against this protein are found in a subset of patients with dermatomyositis. Three alternatively spliced transcripts encoding different isoforms have been described. Mutations in CHD3 cause a neurodevelopmental syndrome (Snijders Blok-Campeau syndrome) with macrocephaly and impaired speech and language. Interactions CHD3 has been shown to interact with: * HDAC1, * Histone deacetylase 2 and * SERBP1 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Induced Pluripotent Stem Cell
Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes (named Myc, Oct3/4, Sox2 and Klf4), collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent." Pluripotent stem cells hold promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease. The most well-known type of pluripotent stem cell is the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Histone Deacetylase 2
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the ''HDAC2'' gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones (H2A, H2B, H3, and H4). As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy. Though the functional role of the class to which HDAC2 belongs has been carefully studied, the mechanism by which HDAC2 interacts with histone deacetylases of other classes has yet to be elucidated. HDAC2 is broadly regulated by protein kinase 2 (CK2) and protein phosphatase 1 (PP1), but biochemical analysis suggests its regulation is more complex (evinced by the coexistence of HDAC1 and HDAC2 in three distinct protein complexes). Essentially, the mechanism by which HDAC2 is regulated is still unclear b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC2
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the ''HDAC2'' gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones (H2A, H2B, H3, and H4). As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy. Though the functional role of the class to which HDAC2 belongs has been carefully studied, the mechanism by which HDAC2 interacts with histone deacetylases of other classes has yet to be elucidated. HDAC2 is broadly regulated by protein kinase 2 (CK2) and protein phosphatase 1 (PP1), but biochemical analysis suggests its regulation is more complex (evinced by the coexistence of HDAC1 and HDAC2 in three distinct protein complexes). Essentially, the mechanism by which HDAC2 is regulated is still unclear by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RBBP7
Histone-binding protein RBBP7 is a protein that in humans is encoded by the ''RBBP7'' gene. Function This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that binds directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation. Model organisms Model organisms have been used in the study of RBBP7 function. A conditional knockout mouse line, called ''Rbbp7tm1a(EUCOMM)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interes ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CHD4
Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the ''CHD4'' gene. Function The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Patients with dermatomyositis develop antibodies against this protein. Interactions CHD4 has been shown to interact with HDAC1, Histone deacetylase 2, MTA2, SATB1 and Ataxia telangiectasia and Rad3 related. Clinical Mutations in this gene have been associated with a condition known as Sifrim-Hitz-Weiss syndrome.Weiss K, Lazar HP, Kurolap A, Martinez AF, Paperna T, Cohen L, Smeland MF, Wallen S, Solveig H, Keren B, Terhal P, Irving M, Takaku M, Roberts JD, Petrovich RM, Schrier Vergano SA11,12, Kenney A11, Hove H13, DeChene E, Quinonez SC, Colin E, Ziegler A, Rumple M, Jain M, Monteil D, Roeder ER, Nugent K, van Haeringen A, Gambello M, Sant ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
.jpg "Click for more on -> Induced Pluripotent Stem Cell")