Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H, M, R, Rb||ICC, IP, WB||M||Purified||Monoclonal Antibody|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Stable for 1 year at 2-8°C from date of receipt.|
|Material Size||100 µg|
|Anti-Bmi-1, clone F6||2462874|
|Anti-Bmi-1, clone F6 (mouse monoclonal IgG1) Monoclonal Antibody||Q2922299|
|Anti-Bmi-1, clone F6 - 2153145||2153145|
|Anti-Bmi-1, clone F6 - 2382167||2382167|
|Anti-Bmi-1, clone F6 - 2430420||2430420|
|Anti-Bmi-1, clone F6 - 1624901||1624901|
|Anti-Bmi-1, clone F6 - 1957274||1957274|
|Anti-Bmi-1, clone F6 - 1975350||1975350|
|Anti-Bmi-1, clone F6 - 2019726||2019726|
|Anti-Bmi-1, clone F6 - 22103||22103|
|Reference overview||Application||Species||Pub Med ID|
|A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells.|
Mao, DD; Gujar, AD; Mahlokozera, T; Chen, I; Pan, Y; Luo, J; Brost, T; Thompson, EA; Turski, A; Leuthardt, EC; Dunn, GP; Chicoine, MR; Rich, KM; Dowling, JL; Zipfel, GJ; Dacey, RG; Achilefu, S; Tran, DD; Yano, H; Kim, AH
Cell reports 1809-21 2015
Glioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma.
|Immunoblotting (Western), Chromatin Immunoprecipitation (ChIP)||26074073|
|Retrovirus-Mediated Expression of E2A-PBX1 Blocks Lymphoid Fate but Permits Retention of Myeloid Potential in Early Hematopoietic Progenitors.|
Woodcroft, MW; Nanan, K; Thompson, P; Tyryshkin, K; Smith, SP; Slany, RK; LeBrun, DP
PloS one 10 e0130495 2015
The oncogenic transcription factor E2A-PBX1 is expressed consequent to chromosomal translocation 1;19 and is an important oncogenic driver in cases of pre-B-cell acute lymphoblastic leukemia (ALL). Elucidating the mechanism by which E2A-PBX1 induces lymphoid leukemia would be expedited by the availability of a tractable experimental model in which enforced expression of E2A-PBX1 in hematopoietic progenitors induces pre-B-cell ALL. However, hematopoietic reconstitution of irradiated mice with bone marrow infected with E2A-PBX1-expressing retroviruses consistently gives rise to myeloid, not lymphoid, leukemia. Here, we elucidate the hematopoietic consequences of forced E2A-PBX1 expression in primary murine hematopoietic progenitors. We show that introducing E2A-PBX1 into multipotent progenitors permits the retention of myeloid potential but imposes a dense barrier to lymphoid development prior to the common lymphoid progenitor stage, thus helping to explain the eventual development of myeloid, and not lymphoid, leukemia in transplanted mice. Our findings also indicate that E2A-PBX1 enforces the aberrant, persistent expression of some genes that would normally have been down-regulated in the subsequent course of hematopoietic maturation. We show that enforced expression of one such gene, Hoxa9, a proto-oncogene associated with myeloid leukemia, partially reproduces the phenotype produced by E2A-PBX1 itself. Existing evidence suggests that the 1;19 translocation event takes place in committed B-lymphoid progenitors. However, we find that retrovirus-enforced expression of E2A-PBX1 in committed pro-B-cells results in cell cycle arrest and apoptosis. Our findings indicate that the neoplastic phenotype induced by E2A-PBX1 is determined by the developmental stage of the cell into which the oncoprotein is introduced.
|Silencing BMI1 eliminates tumor formation of pediatric glioma CD133+ cells not by affecting known targets but by down-regulating a novel set of core genes.|
Baxter, PA; Lin, Q; Mao, H; Kogiso, M; Zhao, X; Liu, Z; Huang, Y; Voicu, H; Gurusiddappa, S; Su, JM; Adesina, AM; Perlaky, L; Dauser, RC; Leung, HC; Muraszko, KM; Heth, JA; Fan, X; Lau, CC; Man, TK; Chintagumpala, M; Li, XN
Acta neuropathologica communications 2 160 2014
Clinical outcome of children with malignant glioma remains dismal. Here, we examined the role of over-expressed BMI1, a regulator of stem cell self-renewal, in sustaining tumor formation in pediatric glioma stem cells. Our investigation revealed BMI1 over-expression in 29 of 54 (53.7%) pediatric gliomas, 8 of 8 (100%) patient derived orthotopic xenograft (PDOX) mouse models, and in both CD133+ and CD133- glioma cells. We demonstrated that lentiviral-shRNA mediated silencing of suppressed cell proliferation in vitro in cells derived from 3 independent PDOX models and eliminated tumor-forming capacity of CD133+ and CD133- cells derived from 2 PDOX models in mouse brains. Gene expression profiling showed that most of the molecular targets of BMI1 ablation in CD133+ cells were different from that in CD133- cells. Importantly, we found that silencing BMI1 in CD133+ cells derived from 3 PDOX models did not affect most of the known genes previously associated with the activated BMI1, but modulated a novel set of core genes, including RPS6KA2, ALDH3A2, FMFB, DTL, API5, EIF4G2, KIF5c, LOC650152, C20ORF121, LOC203547, LOC653308, and LOC642489, to mediate the elimination of tumor formation. In summary, we identified the over-expressed BMI1 as a promising therapeutic target for glioma stem cells, and suggest that the signaling pathways associated with activated BMI1 in promoting tumor growth may be different from those induced by silencing BMI1 in blocking tumor formation. These findings highlighted the importance of careful re-analysis of the affected genes following the inhibition of abnormally activated oncogenic pathways to identify determinants that can potentially predict therapeutic efficacy.
|Psip1/Ledgf p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins.|
Pradeepa, MM; Grimes, GR; Taylor, GC; Sutherland, HG; Bickmore, WA
Nucleic acids research 42 9021-32 2014
Trithorax and polycomb group proteins are generally thought to antagonize one another. The trithorax family member MLL (myeloid/lymphoid or mixed-lineage leukemia) is presumed to activate Hox expression, counteracting polycomb-mediated repression. PC4 and SF2 interacting protein 1 (PSIP1)/p75, also known as LEDGF, whose PWWP domain binds to H3K36me3, interacts with MLL and tethers MLL fusion proteins to HOXA9 in leukaemias. Here we show, unexpectedly, that Psip1/p75 regulates homeotic genes by recruiting not only MLL complexes, but also the polycomb group protein Bmi1. In Psip1(-/-) cells binding of Mll1/2, Bmi1 and the co-repressor Ctbp1 at Hox loci are all abrogated and Hoxa and Hoxd mRNA expression increased. Our data not only reveal a potential mechanism of action for Psip1 in the regulation of Hox genes but also suggest an unexpected interplay between proteins usually considered as transcriptional activators and repressors.
|Ring1b bookmarks genes in pancreatic embryonic progenitors for repression in adult β cells.|
van Arensbergen, J; García-Hurtado, J; Maestro, MA; Correa-Tapia, M; Rutter, GA; Vidal, M; Ferrer, J
Genes & development 27 52-63 2013
Polycomb-mediated gene repression is essential for embryonic development, yet its precise role in lineage-specific programming is poorly understood. Here we inactivated Ring1b, encoding a polycomb-repressive complex 1 subunit, in pancreatic multipotent progenitors (Ring1b(progKO)). This caused transcriptional derepression of a subset of direct Ring1b target genes in differentiated pancreatic islet cells. Unexpectedly, Ring1b inactivation in differentiated islet β cells (Ring1b(βKO)) did not cause derepression, even after multiple rounds of cell division, suggesting a role for Ring1b in the establishment but not the maintenance of repression. Consistent with this notion, derepression in Ring1b(progKO) islets occurred preferentially in genes that were targeted de novo by Ring1b during pancreas development. The results support a model in which Ring1b bookmarks its target genes during embryonic development, and these genes are maintained in a repressed state through Ring1b-independent mechanisms in terminally differentiated cells. This work provides novel insights into how epigenetic mechanisms contribute to shaping the transcriptional identity of differentiated lineages.
|Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas.|
Ko, SB; Azuma, S; Yokoyama, Y; Yamamoto, A; Kyokane, K; Niida, S; Ishiguro, H; Ko, MS
American journal of physiology. Gastrointestinal and liver physiology 304 G1103-16 2013
We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4⁺) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4⁺ cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4⁺ cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas.
|Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks.|
Holdt, LM; Hoffmann, S; Sass, K; Langenberger, D; Scholz, M; Krohn, K; Finstermeier, K; Stahringer, A; Wilfert, W; Beutner, F; Gielen, S; Schuler, G; Gäbel, G; Bergert, H; Bechmann, I; Stadler, PF; Thiery, J; Teupser, D
PLoS genetics 9 e1003588 2013
The chromosome 9p21 (Chr9p21) locus of coronary artery disease has been identified in the first surge of genome-wide association and is the strongest genetic factor of atherosclerosis known today. Chr9p21 encodes the long non-coding RNA (ncRNA) antisense non-coding RNA in the INK4 locus (ANRIL). ANRIL expression is associated with the Chr9p21 genotype and correlated with atherosclerosis severity. Here, we report on the molecular mechanisms through which ANRIL regulates target-genes in trans, leading to increased cell proliferation, increased cell adhesion and decreased apoptosis, which are all essential mechanisms of atherogenesis. Importantly, trans-regulation was dependent on Alu motifs, which marked the promoters of ANRIL target genes and were mirrored in ANRIL RNA transcripts. ANRIL bound Polycomb group proteins that were highly enriched in the proximity of Alu motifs across the genome and were recruited to promoters of target genes upon ANRIL over-expression. The functional relevance of Alu motifs in ANRIL was confirmed by deletion and mutagenesis, reversing trans-regulation and atherogenic cell functions. ANRIL-regulated networks were confirmed in 2280 individuals with and without coronary artery disease and functionally validated in primary cells from patients carrying the Chr9p21 risk allele. Our study provides a molecular mechanism for pro-atherogenic effects of ANRIL at Chr9p21 and suggests a novel role for Alu elements in epigenetic gene regulation by long ncRNAs.
|Knockdown BMI1 expression inhibits proliferation and invasion in human bladder cancer T24 cells.|
Liang, W; Zhu, D; Cui, X; Su, J; Liu, H; Han, J; Zhao, F; Xie, W
Molecular and cellular biochemistry 382 283-91 2013
B cell-specific moloney murine leukemia virus integration site 1 (BMI1) is a transcriptional repressor of polycomb repressive complex 1, which is involved in the proliferation, senescence, migration, and tumorigenesis of cancer. Experimental researchers have convincingly linked BMI1 to tumorigenesis. However, there is no study about the issue on the role of BMI1 in the proliferation, apoptosis, and migration of bladder cancer. To address this question, we examined the expression of BMI1 in bladder cancer tissues and used siRNA to knockdown BMI1 expression in bladder cancer T24 cells. Then we tested the cell proliferation by CCK8 assay and soft agar colony formation assay, apoptosis by flow cytometry assay, and cell invasiveness by transwell migration assay. Our results revealed that BMI1 promoted proliferation, migration, invasion, and progression in bladder cancer. Over-expression of BMI1 was correlated with tumor clinic-pathological features. BMI1 siRNA effectively inhibited bladder cancer cell proliferation and migration in vitro, and it promoted bladder cancer invasion, maybe by causing epithelial-to-mesenchymal transition. Our findings suggested that BMI1 may represent a novel diagnostic marker and a therapeutic target for bladder cancer, and deserves further investigation.
|Combined modulation of polycomb and trithorax genes rejuvenates β cell replication.|
Zhou, JX; Dhawan, S; Fu, H; Snyder, E; Bottino, R; Kundu, S; Kim, SK; Bhushan, A
The Journal of clinical investigation 123 4849-58 2013
Inadequate functional β cell mass underlies both type 1 and type 2 diabetes. β Cell growth and regeneration also decrease with age through mechanisms that are not fully understood. Age-dependent loss of enhancer of zeste homolog 2 (EZH2) prevents adult β cell replication through derepression of the gene encoding cyclin-dependent kinase inhibitor 2a (INK4a). We investigated whether replenishing EZH2 could reverse the age-dependent increase of Ink4a transcription. We generated an inducible pancreatic β cell-specific Ezh2 transgenic mouse model and showed that transgene expression of Ezh2 was sufficient to increase β cell replication and regeneration in young adult mice. In mice older than 8 months, induction of Ezh2 was unable to repress Ink4a. Older mice had an enrichment of a trithorax group (TrxG) protein complex at the Ink4a locus. Knockdown of TrxG complex components, in conjunction with expression of Ezh2, resulted in Ink4a repression and increased replication of β cells in aged mice. These results indicate that combined modulation of polycomb group proteins, such as EZH2, along with TrxG proteins to repress Ink4a can rejuvenate the replication capacity of aged β cells. This study provides potential therapeutic targets for expansion of adult β cell mass.
|Transcription factors FOXG1 and Groucho/TLE promote glioblastoma growth.|
Verginelli, F; Perin, A; Dali, R; Fung, KH; Lo, R; Longatti, P; Guiot, MC; Del Maestro, RF; Rossi, S; di Porzio, U; Stechishin, O; Weiss, S; Stifani, S
Nature communications 4 2956 2013
Glioblastoma (GBM) is the most common and deadly malignant brain cancer, with a median survival of less than 2 years. GBM displays a cellular complexity that includes brain tumour-initiating cells (BTICs), which are considered as potential key targets for GBM therapies. Here we show that the transcription factors FOXG1 and Groucho/TLE are expressed in poorly differentiated astroglial cells in human GBM specimens and in primary cultures of GBM-derived BTICs, where they form a complex. FOXG1 knockdown in BTICs causes downregulation of neural stem/progenitor and proliferation markers, increased replicative senescence, upregulation of astroglial differentiation genes and decreased BTIC-initiated tumour growth after intracranial transplantation into host mice. These effects are phenocopied by Groucho/TLE knockdown or dominant inhibition of the FOXG1:Groucho/TLE complex. These results provide evidence that transcriptional programmes regulated by FOXG1 and Groucho/TLE are important for BTIC-initiated brain tumour growth, implicating FOXG1 and Groucho/TLE in GBM tumourigenesis.