PRDM1 (PR domain containing 1, with ZNF domain)

2011-09-01   Wayne Tam 

Department of Pathology, Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA




Atlas Image
Figure 1.


The gene encompasses 23,6 kb DNA in humans, from 106534195 to 106557814 (hg19-Feb, 2009) in the long arm of chromosome 6. It encodes 7 exons. The open reading frame spans all 7 exons.


The mRNAs encoded by PRDM1 have two transcript isoforms, PRDM1alpha and PRDM1beta, which are 5164 and 4675 bp long, respectively. The shorter isoform is generated by usage of the alternative promoter located in intron 3 and contains a different 5 untranslated region. It lacks the 5 inframe portion of the coding region present in PRDM1alpha. A deletion exon 6 (exon 7 in mice) variant has also been described (Schmidt et al., 2008).





PRDM1alpha is the larger isoform and contains 825 amino acids, with a predicted molecular weight of 92 kD. It has a PR domain at the N-terminal portion (86-207 aa) of the protein, which is related to the SET domain (SM00317, SMART) found in many histone methyltransferases. In contrast to bona fide SET-domain proteins, the PR domain in PRDM1 does not possess intrinsic histone methyltransferase activity. Five C2H2-type zinc fingers (SM00355, SMART), which represent the DNA binding domain, are present at the C-terminal portion of the protein (575-707 aa). The middle part of PRDM1 (about 300-400 aa) is rich in proline and serine. PRDM1beta lacks the N-terminal 101 amino acids of the PRDM1alpha, and has a truncated PR domain. PRDM1beta has been shown to be functionally impaired in its transcriptional repression activity (Gyory et al., 2003). The proximal 3 zinc fingers in PRDM1/Blimp-1 delta exon 6 variant are disrupted (Schmidt et al., 2008). This protein variant has auto-regulatory potential through negative regulation of PRDM1/Blimp-1 expression and functions.
Atlas Image
Figure 2.


PRDM1/Blimp-1 is expressed in several tissues and organs, including hematopoietic tissues, skin, central nervous system, testis and gut. Within the hematopoitic system, PRDM1/Blimp-1 is expressed in plasma cells, B cells, T cells, natural killer cells, monocytes, granulocytes and dendritic cells. In the B cell population, PRDM1/Blimp-1 starts to be expressed when they are committed to undergo terminal differentiation (Cattoretti et al., 2005). Consistent with its expression in normal lymphoid cells, PRDM1 is also expressed in 100% of multiple myeloma, and in various frequency in B and T lymphomas (Garcia et al., 2006; DCosta et al., 2009). PRDM1/Blimp-1 expression is regulated by a number of transcription activators and repressors (Martins and Calame, 2008). MicroRNAs have also been implicated in the down-regulation of PRDM1 in both normal germinal center B cells (Malumbres et al., 2009; Zhang et al., 2009; Gururajan et al., 2010) and in neoplastic lymphoid cells (Nie et al., 2008; Nie et al., 2010). Among PRDM1 isoforms, PRDM1alpha is the most abundantly expressed, although relative abundance between PRDM1alpha and PRDM1beta may vary between cell types (Garcia et al., 2006). PRDM1/Blimp-1 delta 6 isoform is preferentially expressed in resting B cells (Schmidt et al., 2008).




Mechanisms of action
PRDM1/Blimp-1 is a transcription repressor that binds to specific DNA sequences through its zinc fingers, and functions as a scaffold for recruiting co-repressors that catalyze histone modifications. It has no known intrinsic histone methyltransferase activity. PRDM1/blimp-1 has been shown to mediate transcriptional silencing via interactions with H3 lysine methyltransferase G9a (Gyory et al., 2004), histone deacetylases HDAC1 and HDAC2 (Yu et al., 2000), and H3 lysine demethylase LSD1 (Su et al., 2009). PRDM1 can also tether Groucho family of transcription factors to mediate repression of gene transcription (Ren et al., 1999). Interaction of PRDM1/Blimp-1 with these co-repressors is mediated through the proline/serine rich domain and/or the zinc fingers. PRDM1 exerts its biological functions by repressing expressions of various target genes, which can be cell-type specific. For example, PRDM1/Blimp-1 mediates cell-cycle arrest in B cells by repressing c-myc, and in CD4 positive helper T cells by inhibiting expressions of IL-2 and Fos, an IL-2 activator (Martins and Calame, 2008).
Biologic functions
PRDM1 was originally identified as a novel repressor of human beta-interferon gene expression called PRDI-BF1 (positive regulatory domain I binding factor 1) (Keller and Maniatis, 1991). Later Blimp-1 (B lymphocyte-induced maturation protein), which represents the murine homolog of PRDI-BF1(Huang, 1994), was discovered as a protein the enforced expression of which was sufficient to drive plasma cell differentiation of a mouse lymphoma cell line with an activated B cell phenotype (Turner et al., 1994). Studies since then have revealed a role of PRDM1/Blimp-1 in multiple cell types.
PRDM1/Blimp-1 is the master regulator of plasma cell differentiation, critical for the generation of immunoglobulin-secreting plasma cells and maintenance of long-lived plasma cells (Shapiro-Shelef et al., 2003; Shapiro-Shelef et al., 2005; Martins and Calame, 2008). It mediates terminal B cell differentiation by extinguishing gene programs related to B cell signaling and proliferation (Shaffer et al., 2002), and allowing induction of XBP1 which coordinates phenotypic changes, including expansion of endoplasmic reticulum and increased protein synthesis, that define the plasma cell phenotype (Shaffer et al., 2004).
PRDM1/Blimp-1 is also required for T cell homeostasis (Kallies et al., 2006; Martins et al., 2006; Calame, 2010). It attenuates proliferation and survival of CD4 positive helper T cells by repressing IL-2-dependent activation; inhibits Th1 differentiation by down-regulating IFNgamma, Tbx21 and BCL6; and antagonizes BCL6-dependent follicular T cell differentiation. PRDM1/Blimp-1 also plays critical role in the differentiation of CD8-positive T cells.
Besides its critical functions in B and T cells, PRDM1/Blimp-1 promotes differentiation of macrophages (Chang et al., 2000). It is also important for homeostatic development of dendritic cells as well as dendritic cell maturation (Chan et al., 2009). PRDM1/Blimp-1 negatively regulates NK cell activation by suppressing effector cytokine production (Smith et al., 2010).
In the non-hematopoietic cell types, PRDM1/Blimp-1 plays an important role in the terminal differentiation of keratinocytes (Magnusdottir et al., 2007) and sebaceous cells (Sellheyer and Krahl, 2010). It also regulates postnatal reprogramming of intestinal enterocytes (Harper et al., 2011).
Furthermore, PRDM1/Blimp-1 is required in embryonic developmental cell fate specification and organ morphogenesis, as demonstrated by mouse and zebrafish model systems (Bikoff et al., 2009). Blimp-1 specifies cell fate of primordial germ cells (Vincent et al., 2005), neural crests and neuron progenitors (Roy and Ng, 2004), and also muscle fiber identity (Baxendale et al., 2004; Hofsten et al., 2008). Blimp-1 is also critical for the normal development of the cardiovascular system, forelimbs and vibrissae (Robertson et al., 2007).


PRDM1 is conserved in chimpanzee, dog, cow, mouse, rat, chicken and zebrafish.



Somatic mutations have been identified in diffuse large B cell lymphomas (DLBCL) at a frequency of about 8 to 23% (Tam et al., 2006; Pasqualucci et al., 2006; Mandelbaum et al., 2010). One group did not detect mutations in 82 cases of DLBCLs in the Chinese population, suggesting geographic differences in PRDM1 mutations in DLBCL (Liu et al., 2007). PRDM1 mutations are exclusively detected in about 24 to 35% of the activated B cell(ABC)/non-germinal center B cell (non-GCB) subtype of DLBCL, and have not been identified in GCB-like DLBCL. In addition, about 20% of primary DLBCL of the central nervous system, a subtype of DLBCL, harbor PRDM1 mutations (Courts et al., 2008). PRDM1 mutation was also found in one case of primary effusion lymphoma out of 2 cases analyzed (Tate et al., 2007). The types of somatic mutations seen in PRDM1 include splice site mutations, frameshift insertion/deletion and less frequently, nonsense and missense mutations. The vast majority of these mutations result in inactivating truncations lacking one or more of the critical domains including PR, proline rich region, and the zinc fingers. Missense mutations have been demonstrated to affect PRDM1 functions (Mandelbaum et al., 2010). Most of the somatic mutations (about 90%) are associated with inactivation of the other allele by deletion, consistent with biallelic inactivation characteristic of a tumor suppressor gene. Mutations in acute leukemias and solid tumors have been not identified (Hangaishi and Kurokawa, 2010).

Implicated in

Diffuse large B cell lymphoma (DLBCL) with partial plasmablastic differentiation, as indicated by PRDM1 expression, has a worse overall and failure free survival compared to conventional DLBLC without PRDM1 expression, suggesting that PRDM1 may be useful as a prognostic marker in DLBCL (Montes-Moreno et al., 2010).
Expression of PRDM1beta has been implicated as a poor prognostic marker in DBLCL treated with CHOP (but not R-CHOP) and in T cell lymphomas. Resistance to chemotherapeutic agents mediated by PRDM1beta has been proposed as a potential mechanism (Liu et al., 2007; Zhao et al., 2008).
Inactivation or down-regulation of PRDM1 appears to be an important event in the pathogenesis of DLBCLs of the ABC/non-GCB subtype. In about 50% of DLBCLs of this subtype, PRDM1 is inactivated by truncating or missense mutations, biallele gene deletions or transcription repression by a constitutively active, translocated BCL6 (Mandelbaum et al., 2010). In non-GCB/ABC-like DLBCL without these genetic lesions, asynchronous PRDM1 mRNA and protein expressions have been observed, suggesting a post-transcriptional down-regulation (Mandelbaum et al., 2010; Nie et al., 2010). MicroRNAs have been postulated as a potential mechanism of down-regulation (Nie et al., 2010). All these findings are consistent with a tumor suppressor role of PRDM1 in DLBCL. In addition, PRDM1/Blimp-1 has been directly demonstrated in mouse models to function as a tumor suppressor gene (Calado et al., 2010; Mandelbaum et al., 2010). Mice lacking PRDM1/Blimp-1 are predisposed to develop lymphoproliferative disorders resembling human ABC-like DLBCL. One of these mouse models also demonstrated a cooperative pathogenic effect between PRDM1 inactivation and constitutive NF-kB activation. These findings suggest that PRDM1 inactivation contributes to the pathogenesis of ABC-like DLBCL by inhibiting terminal B cell differentiation induced by constitutive canonical NF-kB activation characteristically present in this lymphoma type.
PRDM1 is frequently (about 40%) deleted as part of a minimal deleted region in aggressive natural killer (NK) cell neoplasms such as extranodal NK/T cell lymphomas, nasal type, and aggressive NK cell leukemias (Iqbal et al., 2009; Karube et al., 2011). This deletion is generally associated with a down-regulation of PRDM1 expression, associated with focal hypermethylation of the 5 region of the other PRDM1 allele. Enforced expression of PRDM1 in NK lymphoma cell lines results in cell cycle arrest and apoptosis (Karube et al., 2011). Inactivating nonsense mutations have also been found in two NK cell lines and one clinical NK neoplasm (Iqbal et al., 2009; Karube et al., 2011). These findings indicate a tumor suppressor role of PRDM1 in NK cell neoplasms.
Entity name
Radiation-therapy induced second malignant neoplasms
Pediatric Hodgkin lymphoma patients treated by radiation are at risk of developing second malignancies later in life. Two SNP variants were identified at 6q21 (intergenic between ATG5 and PRDM1) in a genome wide association study that are associated with increased risk of second neoplasms for pediatric patients with Hodgkin lymphoma who received radiation therapy. These variants correlate with decreased basal PRDM1 expression and reduced PRDM1 induction after radiation therapy, implicating PRDM1 in the etiology of radiation-therapy induced second malignancies (Best et al., 2011).
PRDM1 is consistently expressed in plasma cell myeloma. A plasmacytoma transgenic mouse model demonstrates that PRDM1/Blimp-1 is not a tumor suppressor gene in myeloma. Instead, it appears to be a limiting factor in plasma cell transformation (DCosta et al., 2009). Reducing PRDM1/Blimp-1 dosage decreases incidence of plasmacytoma in mice but does not cause reduction of normal plasma cells in nontransgenic mice. Loss of PRDM1/Blimp-1 eliminates plasmacytoma development.


Pubmed IDLast YearTitleAuthors
147020442004The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling.Baxendale S et al
217854312011Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma.Best T et al
195922322009An expanding job description for Blimp-1/PRDM1.Bikoff EK et al
211562822010Constitutive canonical NF-κB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma.Calado DP et al
205622662010Blimp-1's maiden flight.Calame K et al
157729842005PRDM1/Blimp-1 is expressed in human B-lymphocytes committed to the plasma cell lineage.Cattoretti G et al
199150492009Absence of the transcriptional repressor Blimp-1 in hematopoietic lineages reveals its role in dendritic cell homeostatic development and function.Chan YH et al
112488112000BLIMP-1: trigger for differentiation of myeloid lineage.Chang DH et al
185965412008Recurrent inactivation of the PRDM1 gene in primary central nervous system lymphoma.Courts C et al
193297822009Blimp1 is limiting for transformation in a mouse plasmacytoma model.D'Costa K et al
165850132006PRDM1/BLIMP-1 expression in multiple B and T-cell lymphoma.Garcia JF et al
204979602010MicroRNA 125b inhibition of B cell differentiation in germinal centers.Gururajan M et al
126265692003Identification of a functionally impaired positive regulatory domain I binding factor 1 transcription repressor in myeloma cell lines.Györy I et al
149857132004PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing.Gyory I et al
200470962010Blimp-1 is a tumor suppressor gene in lymphoid malignancies.Hangaishi A et al
216702992011The transcriptional repressor Blimp1/Prdm1 regulates postnatal reprogramming of intestinal enterocytes.Harper J et al
80332161994Blimp-1 is the murine homolog of the human transcriptional repressor PRDI-BF1.Huang S et al
191944642009Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies.Iqbal J et al
165657202006Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self-tolerance.Kallies A et al
216905542011Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses.Karube K et al
18511231991Identification and characterization of a novel repressor of beta-interferon gene expression.Keller AD et al
173797442007Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma.Liu YY et al
178464222007Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1.Magnúsdóttir E et al
190476782009Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas.Malumbres R et al
211562812010BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma.Mandelbaum J et al
183709212008Regulation and functions of Blimp-1 in T and B lymphocytes.Martins G et al
165657212006Transcriptional repressor Blimp-1 regulates T cell homeostasis and function.Martins GA et al
204182452010Aggressive large B-cell lymphoma with plasma cell differentiation: immunohistochemical characterization of plasmablastic lymphoma and diffuse large B-cell lymphoma with partial plasmablastic phenotype.Montes-Moreno S et al
185833252008MicroRNA-mediated down-regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg cells: a potential pathogenetic lesion in Hodgkin lymphomas.Nie K et al
206512442010Epigenetic down-regulation of the tumor suppressor gene PRDM1/Blimp-1 in diffuse large B cell lymphomas: a potential role of the microRNA let-7.Nie K et al
164928052006Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma.Pasqualucci L et al
98871051999PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins.Ren B et al
180399672007Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice.Robertson EJ et al
154586502004Blimp-1 specifies neural crest and sensory neuron progenitors in the zebrafish embryo.Roy S et al
188451442008Blimp-1Deltaexon7: a naturally occurring Blimp-1 deletion mutant with auto-regulatory potential.Schmidt D et al
197884432010Blimp-1: a marker of terminal differentiation but not of sebocytic progenitor cells.Sellheyer K et al
153452222004XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation.Shaffer AL et al
163144382005Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow.Shapiro-Shelef M et al
209440052010PRDM1/Blimp-1 controls effector cytokine production in human NK cells.Smith MA et al
191246092009Involvement of histone demethylase LSD1 in Blimp-1-mediated gene repression during plasma cell differentiation.Su ST et al
164243922006Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas.Tam W et al
172130242007Novel BLIMP1/PRDM1 gene mutations in B-cell lymphoma.Tate G et al
81681361994Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells.Turner CA Jr et al
157501842005The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse.Vincent SD et al
107131812000Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase.Yu J et al
192021282009Patterns of microRNA expression characterize stages of human B-cell differentiation.Zhang J et al
182350462008PRDM1 is involved in chemoresistance of T-cell lymphoma and down-regulated by the proteasome inhibitor.Zhao WL et al
185356252008Prdm1- and Sox6-mediated transcriptional repression specifies muscle fibre type in the zebrafish embryo.von Hofsten J et al

Other Information

Locus ID:

NCBI: 639
MIM: 603423
HGNC: 9346
Ensembl: ENSG00000057657


dbSNP: 639
ClinVar: 639
TCGA: ENSG00000057657


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Expression and DegradationREACTOMER-HSA-6806003
Regulation of TP53 ExpressionREACTOMER-HSA-6804754

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
121508912002Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program.330
198381952009A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.316
198381952009A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.316
183709212008Regulation and functions of Blimp-1 in T and B lymphocytes.145
149857132004PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing.138
198984812009Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk.131
198984812009Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk.131
164928052006Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma.106
190476782009Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas.105
183542042008STAT3-mediated up-regulation of BLIMP1 Is coordinated with BCL6 down-regulation to control human plasma cell differentiation.87


Wayne Tam

PRDM1 (PR domain containing 1, with ZNF domain)

Atlas Genet Cytogenet Oncol Haematol. 2011-09-01

Online version: