DNTTIP1 binds to DNA and increases the activity of TdT. This interaction is significant because TdT adds nucleotides to the V, D, and J exons of T-cell receptor (TCR) and B-cell receptor (BCR) genes during the process of antibody gene recombination. This addition of nucleotides contributes to the phenomenon known as junctional diversity, which is essential for the diversity of the immune response .
In addition to its role in enhancing TdT activity, DNTTIP1 also acts as a transcriptional regulator. It binds to specific DNA sequences and can associate with promoters, such as the RAB20 promoter, to positively regulate transcription. DNTTIP1 has been shown to bind to nucleosomes and may recruit histone deacetylase 1 (HDAC1) complexes to nucleosomes or naked DNA, influencing chromatin structure and gene expression .
The activity of DNTTIP1 and its interaction with TdT are critical for the proper functioning of the immune system. The diversity introduced by TdT during the recombination of TCR and BCR genes allows for a wide variety of antigen receptors, which are necessary for the immune system to recognize and respond to a vast array of pathogens. Studies using TdT knockout mice have demonstrated a significant reduction in TCR diversity, highlighting the importance of TdT and its interacting proteins like DNTTIP1 in immune function .
Mutations or dysregulation of the DNTTIP1 gene have been associated with certain diseases. For example, DNTTIP1 has been linked to nephrotic syndrome, a kidney disorder characterized by excessive protein loss in the urine. Understanding the role of DNTTIP1 in such diseases could provide insights into potential therapeutic targets .
Recombinant human DNTTIP1 is used in various research applications to study its function and interactions. By using recombinant proteins, researchers can investigate the biochemical properties of DNTTIP1, its role in enhancing TdT activity, and its involvement in transcriptional regulation. These studies contribute to a deeper understanding of the molecular mechanisms underlying immune diversity and gene regulation .