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).

None.

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.

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).

Nuclear.

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).