HDAC 7 | Histone deacetylase 7

Histone deacetylase 7 is a thymus-specific, intracellular, transcription factor belonging to the class IIa histone deacetylase family. Reports suggest that dephosphorylation and nuclear localization of HDAC7 is promoted by Myosin phosphatase, thus regulating the repression of Nur77 and inhibition of apoptosis in CD4+CD8+ double-positive thymocytes. HDAC7 plays a specific role in maintaining vascular integrity by repressing the expression of matrix metalloproteinase (MMP) 10. It promotes repression mediated by transcriptional co repressor NCOR2 and is an efficient co repressor of the androgen receptor (AR). It is also responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

DNMT | DNA Methyl transferase

Common epigenetic modifications found in eukaryotic organisms ranging from fungi to mammals include DNA methylation which is mainly performed by DNA methyltransferase (DNMT). DNMT is an enzyme responsible for generating and maintaining DNA methylation patterns that control different genome functions. DNMT enzymes exhibit distinct biochemical properties and biological functions, due to their structural differences. The highly variable N-terminal extensions of these nuclear proteins harbor various evolutionarily conserved domains and motifs, some of which have been shown to be involved in functional specializations. In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. In eukaryotes, DNA methylation has been implicated in the control of several cellular processes, including differentiation, gene regulation, and embryonic development. Recent findings also suggest an important role of DNMT in oncogenesis and its importance as a candidate target for anticancer therapy.

DNMT 3B | DNA Methyl transferase 3B

DNMT3B well known as DNA (cytosine-5)-methyltransferase 3B is a nuclear protein belonging to the C5-methyltransferase family with an ADD-type zinc finger and a PWWP domain. This DNA associated enzyme is essential for genome wide de novo methylation and is required for development (at least in mouse) and catalytically methylating cytosines in CpG pairs. DNA methylation is coordinated with methylation of histones. Out of the six isoforms reported isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. DNMT3B forms a universal repressor complex containing DNMT3B and ZHX1. It interacts with other proteins like HDAC1, HDAC2, HP1 proteins, SUV39H1, and components of the histone methylation system, the ATP-dependent chromatin remodeling enzyme SMARCA5. Ubiquitously expressed in most of the tissues. Defects in DNMT3B are a cause of a rare autosomal recessive disorder immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) biochemically characterized by hypomethylation of CpG sites in some regions of heterochromatin.

NMT 1 | DNA Methyl transferase 1

DNMT1 well known as DNA (cytosine-5)-methyltransferase 1 is a 1616 amino acid containing nuclear protein that methylates CpG residues. DNMT1 belongs to the C5-methyltransferase family with two BAH domains and a CXXC-type zinc finger. It is known to preferentially methylate hemimethylated DNA and is also responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Direct interaction between DMAP1, HDAC2 and NMT1 results in the formation of a complex. DNMT1 mediates transcriptional repression by direct binding to HDAC2. Although DNMT1 is known to be ubiquitously expressed in most of the tissues, isoform 2 is less expressed than isoform 1. Moreover its expression is reduced to non detectable levels at the G0 phase of the cell cycle and is dramatically induced upon entrance into the S-phase of the cell cycle.

DNMT3a | DNA Methyl transferase 3a

DNMT3A also known as DNA (cytosine-5)-methyltransferase 3A is a nuclear protein belonging to the C5-methyltransferase family with an ADD-type zinc finger and a PWWP domain. This nuclear protein localizes to euchromatin and is essential for genome wide de novo methylation and is also essential for development. DNA methylation is coordinated with methylation of histones. DNMT3A associates with HDAC1 through its ADD-type zinc-finger. It binds to the ZNF238 transcriptional repressor and is also known to interact with other DNA methyltransferases like DNMT1 and DNMT3B.

DNA topoisomerase I-related function

DNA topoisomerase 1 is a topoisomerase enzyme that catalyzes ATP-independent breakage of single-stranded DNA, followed by passage and rejoining. It catalyzes reaction that leads to the conversion of one topological isomer of DNA to another. Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils. DNA topoisomerase 1 belongs to the eukaryotic type I topoisomerase family and is a monomer known to interact with SV40 Large T antigen that allows viral DNA replication. It is specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity. It generally has diffuse nuclear localization with some enrichment in nucleoli but on CPT treatment, it is cleared from nucleoli into nucleoplasm. Chromosomal aberration involving DNA topoisomerase 1 is found in a form of therapy-related myelodysplastic syndrome.

ATF 2 | Activating transcription factor 2

ATF2 is a nuclear protein detected abundantly in the brain. ATF2 also known as Cyclic AMP-dependent transcription factor ATF-2 is a transcriptional activator that binds DNA as a dimer and can form a homodimer in the absence of DNA. It binds through its N-terminal region to UTF1 which acts as a co activator of ATF2 transcriptional activity. ATF2 belonging to the bZIP family and ATF subfamily has a bZIP domain and a C2H2-type zinc finger. This transcriptional activator binds to the cAMP-responsive element (CRE) which is a consensus sequence present in many viral and cellular promoters. Interaction with JUN redirects JUN to bind to CRES preferentially over the 12-O-tetradecanoylphorbol-13-acetate response elements (TRES) as part of an ATF2-c-Jun complex.