DNMT3A
GeneName
DNMT3A
Summary
DNMT3A is a 102 kDa DNA methyltransferase that is primarily localised in the nucleus and cytoplasm, playing a crucial role in the establishment of DNA methylation patterns during development and cellular differentiation. It is involved in chromatin binding and is essential for genomic imprinting, transcriptional regulation, and the formation of heterochromatin. DNMT3A interacts with various RNA and protein partners, contributing to its function in gene expression regulation and maintaining genomic stability. It is also implicated in cellular responses to environmental stimuli and stressors, including hypoxia and toxic substances.
Importance
DNMT3A is relevant to: - Epigenetic regulation of gene expression, influencing processes such as development and differentiation. - Cancer research, as mutations in DNMT3A are associated with various malignancies, particularly acute myeloid leukaemia. - Neurodevelopmental disorders, given its role in neuron differentiation and potential implications in cognitive functions. - Understanding the mechanisms of genomic imprinting and its implications in inheritance and disease.
Top Products
For researchers investigating DNMT3A, we recommend two primary antibodies that stand out for their performance and reliability. The first is the well-cited polyclonal antibody, Anti-Dnmt3a antibody (ab2850), which has garnered 135 citations, reflecting its strong reputation in the field. This antibody is particularly effective for Western blotting (WB), making it a solid choice for those focused on protein detection.In addition, we offer the recombinant antibody, Anti-Dnmt3a antibody [EPR18455] (ab188470), which has been validated in knockout models and is suitable for a broader range of applications, including WB, immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). With 60 citations, this recombinant product is ideal for researchers seeking consistency and versatility in their experiments. Together, these antibodies provide excellent options for studying DNMT3A in various contexts.
Abcam Product Citation Summary
The data indicates that DNMT3A is being studied in various contexts, particularly in relation to its role in DNA methylation and demethylation processes during adolescence and its interaction with specific RNA molecules. The use of different applications such as Western Blot and immunoprecipitation highlights the importance of this target in understanding epigenetic regulation.
Abcam Product Citation Table
Domain
The PWWP domain is essential for targeting to pericentric heterochromatin. It specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) (By similarity).
Function
Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443). DNA methylation is coordinated with methylation of histones (PubMed:12138111, PubMed:16357870, PubMed:30478443). It modifies DNA in a non-processive manner and also methylates non-CpG sites (PubMed:12138111, PubMed:16357870, PubMed:30478443). May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1 (By similarity). Plays a role in paternal and maternal imprinting (By similarity). Required for methylation of most imprinted loci in germ cells (By similarity). Acts as a transcriptional corepressor for ZBTB18 (By similarity). Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites (By similarity). Can actively repress transcription through the recruitment of HDAC activity (By similarity). Also has weak auto-methylation activity on Cys-710 in absence of DNA (By similarity).
Involvement in disease
Tatton-Brown-Rahman syndrome
TBRS
An overgrowth syndrome characterized by a distinctive facial appearance, tall stature and intellectual disability. Facial gestalt is characterized by a round face, heavy horizontal eyebrows and narrow palpebral fissures. Less common features include atrial septal defects, seizures, umbilical hernia, and scoliosis.
None
The disease is caused by variants affecting the gene represented in this entry.
Leukemia, acute myelogenous
AML
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
None
The disease is caused by variants affecting the gene represented in this entry.
Heyn-Sproul-Jackson syndrome
HESJAS
An autosomal dominant form of microcephalic dwarfism. Affected individuals have intrauterine growth retardation, postnatal growth restrictions, proportionate short stature, microcephaly, severe developmental delay and impaired intellectual development. More variable features include sparse hair, short broad metacarpals and phalanges, and mild recurrent infections.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription.
Auto-methylated at Cys-710: auto-methylation takes place in absence of DNA substrate and inactivates the DNA methyltransferase activity. Inactivation by auto-methylation may be used to inactivate unused DNA methyltransferases in the cell.
Sequence Similarities
Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
Tissue Specificity
Highly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney, and at lower levels in placenta, brain, liver, colon, spleen, small intestine and lung.
Cellular localization
- Nucleus
- Chromosome
- Cytoplasm
- Accumulates in the major satellite repeats at pericentric heterochromatin.
Alternative names
DNA (cytosine-5)-methyltransferase 3A, Dnmt3a, Cysteine methyltransferase DNMT3A, DNA methyltransferase HsaIIIA, DNA MTase HsaIIIA, M.HsaIIIA, DNMT3A