DACH2

Official Full Name

dachshund family transcription factor 2

Organism

Homo sapiens

GeneID

117154

Background

This gene is one of two genes which encode a protein similar to the Drosophila protein dachshund, a transcription factor involved in cell fate determination in the eye, limb and genital disc of the fly. The encoded protein contains two characteristic dachshund domains: an N-terminal domain responsible for DNA binding and a C-terminal domain responsible for protein-protein interactions. This gene is located on the X chromosome and is subject to inactivation by DNA methylation. The encoded protein may be involved in regulation of organogenesis and myogenesis, and may play a role in premature ovarian failure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

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Detailed Information

Dachshund Family Transcription Factor 2 (DACH2) is a member of the highly conserved Dachshund gene family, playing a pivotal role in various biological processes.

Structure And Domain Organization of DACH2

DACH2, a transcription factor, possesses distinctive domains that enable its interactions with DNA, cofactors, and other regulatory proteins. The DACH2 gene is a member of the DAchse (DACH) gene family, encoding proteins with similar structure and function. The DACH2 gene, located on the human chromosome, encodes proteins that are highly conserved, suggesting that it has played a crucial role in evolution.The structural domains of the proteins encoded by the DACH2 gene include a DNA-binding domain and a basic helix-loop-helix (bZIP) domain. These domains enable the DACH2 protein to interact with DNA and proteins to regulate gene expression and cellular function.

Functions of DACH2

This section delves into its diverse roles in various tissues and cell types, elucidating its involvement in organogenesis, tissue homeostasis, and immune responses. DACH2 is involved in a wide array of biological processes, including cell proliferation, differentiation, apoptosis, and tissue development. It plays a crucial role in embryonic development, influencing the formation of various organs and tissues. Additionally, DACH2 is implicated in immune responses and tissue homeostasis, highlighting its multifaceted functions in maintaining cellular equilibrium. DACH2 serves as a transcriptional regulator, influencing critical cellular functions such as proliferation, differentiation, apoptosis, and embryonic development.

DACH2 And Immune Response

DACH2 plays a significant role in the immune response by regulating the expression of various genes involved in inflammation, cell proliferation, and cell fate determination. DACH2's involvement in the immune response stems from its ability to regulate the expression of several key immune-related genes. For instance, it has been shown to activate the expression of anti-inflammatory mediators, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), which help to suppress pro-inflammatory cytokines and maintain immune balance. Additionally, DACH2 can repress the expression of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), thereby contributing to the regulation of immune cell activation and inflammation. Furthermore, It has been reported to regulate the expression of genes involved in lymphoid development, such as the CD4 and CD8 molecules expressed on T-cells, as well as B-cell receptor (BCR) expression. This ultimately impacts the ability of immune cells to recognize and respond to pathogens. In summary, DACH2 serves as a critical regulator of the immune response by modulating the expression of numerous immune-related genes, influencing the development and function of immune cells, and maintaining immune homeostasis.

DACH2 And Cancer

Dachshund Family Transcription Factor 2 (DACH2) has emerged as a crucial player in the regulation of cancer development and progression. DACH2's involvement in cancer primarily stems from its role in regulating cell growth, differentiation, and apoptosis. Studies have shown that DACH2 can suppress the expression of genes involved in cell cycle progression, DNA replication, and angiogenesis, which are key processes underlying tumorigenesis. By regulating these genes, DACH2 helps maintain cellular homeostasis and prevents uncontrolled cell growth. Additionally, DACH2 plays a significant role in DNA repair and oxidative stress response. Impaired DNA repair and increased oxidative stress can lead to genetic mutations and genome instability, which are hallmarks of cancer. Therefore, DACH2's ability to modulate these processes suggests that it may have a protective effect against tumor development. Moreover, DACH2 has been implicated in the regulation of signaling pathways, such as the Wnt/β-catenin, Notch, and Hedgehog pathways, which are often deregulated in cancer. By influencing the activity of these pathways, DACH2 may contribute to the development of tumors.

References:

Macpherson PC, Farshi P, Goldman D. Dach2-Hdac9 signaling regulates reinnervation of muscle endplates. Development. 2015 Dec 1;142(23):4038-48. doi: 10.1242/dev.125674. Epub 2015 Oct 19. PMID: 26483211; PMCID: PMC4712835.
Davis RJ, Pesah YI, Harding M, Paylor R, Mardon G. Mouse Dach2 mutants do not exhibit gross defects in eye development or brain function. Genesis. 2006 Feb;44(2):84-92. doi: 10.1002/gene.20188. PMID: 16470613.

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