PRDM1

Description

The PRDM1 (PR/SET domain 1) is a protein-coding gene located on chromosome 6.

PR domain zinc finger protein 1, or B lymphocyte-induced maturation protein-1 (BLIMP-1), is a protein in humans encoded by the gene PRDM1 located on chromosome 6q21. BLIMP-1 is considered a 'master regulator' of hematopoietic stem cells, and plays a critical role in the development of plasma B cells, T cells, dendritic cells (DCs), macrophages, and osteoclasts. Pattern Recognition Receptors (PRRs) can activate BLIMP-1, both as a direct target and through downstream activation. BLIMP-1 is a transcription factor that triggers expression of many downstream signaling cascades. As a fine-tuned and contextual rheostat of the immune system, BLIMP-1 up- or down-regulates immune responses depending on the precise scenarios. BLIMP-1 is highly expressed in exhausted T-cells – clones of dysfunctional T-cells with diminished functions due to chronic immune response against cancer, viral infections, or organ transplant.

== Function ==

As a potent repressor of beta-interferon (IFN-β), BLIMP-1 competes for interferon regulatory factors (IRF) binding sites in the IFN-β promoter due to its sequence similarity with IRF1 and IRF2. However, BLIMP-1 cools down and activates immune responses in a highly contextual manner. BLIMP-1 represses NFκB/TNF-R pathway repressor NLRP12, thus indirectly activating the immune response. BLIMP-1 expression is also upregulated by danger signals from double-stranded RNA (specific to virus), lipopolysaccharides (specific to gram-negative bacteria), unmethylated CpG DNA (abundant in bacterial genomes), and cancer inflammation via Toll-like receptor (TLR) 3, TLR-4, TLR-9, and STAT signaling, respectively.

PRDM1, also known as BLIMP-1, acts as a transcription factor that regulates gene expression in various immune cell types, including tissue-resident memory T cells (Trm), natural killer (trNK) cells, and natural killer T (NKT) cells. It plays a key role in suppressing the expression of genes that promote the movement of tissue-resident T cells out of non-lymphoid organs, such as the skin, gut, liver, and kidney. This function helps maintain the long-term presence of these cells in these tissues, enabling them to provide rapid immune responses against infections or reinfections. BLIMP-1 directly binds to the PRDI element in the promoter region of the beta-interferon gene. It also promotes the maturation of B lymphocytes into antibody-secreting cells. Additionally, BLIMP-1 interacts with the transcriptional repressor ZNF683, and it acts as a repressor of IRF8, leading to the upregulation of genes involved in osteoclast differentiation, such as NFATC1 and EEIG1.

PRDM1 is also known as BLIMP-1, BLIMP1, PRDI-BF1.

Associated Diseases

WES Whole Exome Sequencing