PRDM1

PRDM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3DAL
Identifiers
Aliases	PRDM1, BLIMP1, PRDI-BF1, PR domain 1, PR/SET domain 1
External IDs	OMIM: 603423 MGI: 99655 HomoloGene: 925 GeneCards: PRDM1
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q21 Start 105,993,463 bp[1] End 106,109,939 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 B2|10 23.24 cM Start 44,437,177 bp[2] End 44,528,501 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • methyltransferase activity • transferase activity • DNA binding • sequence-specific DNA binding • histone deacetylase binding • metal ion binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • GO:0001948 protein binding • nucleic acid binding • promoter-specific chromatin binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • RNA polymerase II transcription regulatory region sequence-specific DNA binding • chromatin DNA binding Cellular component • cytoplasm • nucleus • nucleoplasm Biological process • germ cell development • trophoblast giant cell differentiation • cardiac septum development • cell fate commitment • heart valve development • regulation of transcription, DNA-templated • ventricular septum development • intestinal epithelial cell development • positive regulation of B cell differentiation • embryonic placenta development • in utero embryonic development • negative regulation of transcription by RNA polymerase II • post-embryonic development • coronary vasculature development • negative regulation of gene expression • morphogenesis of a branching structure • transcription, DNA-templated • negative regulation of lipopolysaccharide-mediated signaling pathway • aorta development • methylation • positive regulation of gene expression • maternal placenta development • regulation of cell population proliferation • artery morphogenesis • eye photoreceptor cell development • sebum secreting cell proliferation • negative regulation of B cell proliferation • adaptive immune response • immune system process • regulation of natural killer cell differentiation • regulation of extrathymic T cell differentiation • innate immune response • regulation of NK T cell differentiation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	639	12142
Ensembl	ENSG00000057657	ENSMUSG00000038151
UniProt	O75626	Q60636
RefSeq (mRNA)	NM_001198 NM_182907	NM_007548
RefSeq (protein)	NP_001189 NP_878911	NP_031574
Location (UCSC)	Chr 6: 105.99 – 106.11 Mb	Chr 10: 44.44 – 44.53 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[5] BLIMP-1 is expressed in both B and T cells and plays a significant role in B cell development and antibody production. In B cells, it is a regulator of plasma cell differentiation. In T cells, it is crucial for most terminal effector cell differentiation in CD 4 and CD8 T cells. BLIMP-1 acts as a repressor of beta-interferon (β-IFN) gene expression. The protein binds specifically to the PRDI (positive regulatory domain I element) of the β-IFN gene promoter. Transcription of this gene increases upon virus induction.^[6]

Function[]

BLIMP-1 is an important regulator of plasma cell differentiation. Except for naïve and memory B cells, all antibody secreting cells express BLIMP-1 regardless of their location and differentiation history. In the absence of BLIMP-1, proliferating B cells are unable to differentiate to plasma cells, resulting in severe reduction in production of all isotypes of immunoglobulin. ^[5]

The increased expression of the Blimp-1 protein in B lymphocytes, T lymphocytes, NK cell and other immune system cells leads to an immune response through proliferation and differentiation of antibody secreting plasma cells. Blimp-1 is also considered a 'master regulator' of hematopoietic stem cells.^[7][8] Other cells of the immune system such as human peripheral blood monocytes and granulocytes also express BLIMP-1. In a monocytic cell line, over-expression of BLIMP-1 can lead to differentiation into mature macrophages. BLIMP-1 also plays a role in osteoclastogenesis as well as in the modulation of dendritic cells.

As a transcriptional repressor, BLIMP-1 has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. BLIMP-1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. The genetic lineage-tracing experiments indicate that the BLIMP-1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.^[9]

B cell development[]

During B cell development, a B cell can either differentiate into a short-lived plasma cell or into a germinal center B cell after receiving proper activation and co-stimulation. BLIMP-1 acts as a master gene regulating the transcriptional network that regulates B cell terminal differentiation. BLIMP-1 expression is carefully controlled, since premature expression of it in primary B cells results in cell death. Thus, only cells that are ready to initiate transcription driven by BLIMP-1 are able to survive and differentiate.^[5][10]

T cell development[]

BLIMP-1 plays a key role in maintaining normal T cell homeostasis. It regulates T cell responsiveness through repression of IL-2 cytokine in a negative feedback loop. T cell activation results in production of IL-2. IL-2 signaling then leads to PRDM1 transcription and BLIMP-1 feeds back to repress IL-2 gene transcription.^[5]

T cell exhaustion[]

BLIMP-1 helps the production of short-lived effector T cells and clonally exhausted T cells. It also helps with the migration of T cells out of the spleen and lymph nodes into peripheral tissues. However, BLIMP-1 does not promote the production of long-lived effector memory cells. BLIMP-1 allows the production of some longer lived effector memory cells but its absence allows for the generation of long term central memory cells, which are thought to have a higher potential of proliferation on secondary challenge.^[11]  

Second cancers after radiation treatment[]

A genome-wide association study has identified two genetic variations near the PRDM1 gene that predict an increased likelihood of developing a second cancer after radiation treatment for Hodgkin lymphoma.^[12]

References[]

Further reading[]

External links[]

• PRDM1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook PRDM1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.