Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone

Galli, Giorgio; Lichtenberg, Kristian Honnens de; Carrara, Matteo; Hans, Wolfgang; Wuelling, Manuela; Mentz, Bettina; Multhaupt, Hinke A.B.; Fog, Cathrine K.; Jensen, Kjeld Truberg; Rappsilber, Juri; Vortkamp, Andrea; Coulton, Les; Fuchs, Helmut; Gailus‐Durner, Valérie; Angelis, Martin Hrabé de; Calogero, Raffaele; Couchman, John R.; Lund, Anders H.

doi:10.1371/journal.pgen.1002711

Cited by 52 publications

(77 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21 In line with previous studies, we find PRDM5 to bind a multitude of collagen genes (Supplementary Table S1). 9 In Caco-2 cells, the major collagen targeted is the epithelial COL4A1, rather than COL1A1 as reported in osteoblasts, indicating the cell type-specific target gene recognition of PRDM5. Similarly, we failed to detect the previously published binding to TWIST1 and CDK4 promoters.…”

Section: Discussionmentioning

confidence: 82%

“…9 Towards identifying the mechanistic basis for tumor-suppressive functions of PRDM5, ChIP-sequencing of PRDM5-bound loci in the Caco-2 colon cancer cell line was performed. Caco-2 cells are polarized epithelial cells that grow as normal enterocytes and are often used in drug discovery as models for assaying intestinal epithelial permeability.…”

Section: Discussionmentioning

confidence: 99%

“…9 We analyzed cohorts of Prdm5 LacZ/LacZ animals at different ages but did not observe neoplasias by gross pathology up to the age of 70 weeks. We thereby hypothesized that Prdm5 enhances tumorigenesis driven by the activation of known cancer pathways.…”

Section: Prdm5 Loss Increases Intestinal Adenomas Driven By Apc Mutationmentioning

confidence: 99%

“…Among the responsive genes we identified Adamts9, Col1a1, Mmp13 and Mgll as genes robustly regulated by Prdm5 in MEFs (Figure 4b). Importantly, tumor-suppressor genes such as Adamts9 and Col1a1 were repressed (we recently reported the latter as a functional Prdm5 target in osteoblasts 9 ), whereas genes involved in cancer progression and invasion such as Mmp13 and Mgll were upregulated. We did not detect the differential expression for Dkk1 (Figure 4b), suggesting species-and/or cell-specific regulation of this previously identified target.…”

Section: Mgll Is a Wnt-responsive Gene And A Functional Prdm5 Targetmentioning

confidence: 99%

“…8 Interestingly, PRDM5 silencing has been shown to occur with high frequency in samples from patients with gastric dysplasia or early gastric cancer. 7 Regarding its molecular mechanism, PRDM5 is a sequence-specific transcriptional regulator 2,9 encompassing an N-terminal PR domain, for which no histone methyltransferase activity has been detected, and 16 C 2 H 2 zinc-finger domains mediating protein-DNA and protein-protein interactions. 2 A multitude of genes have been reported to be regulated by PRDM5 including a large repertoire of genes involved in carcinogenesis such as p53, MYC and MDM2, 2,6 although an extensive characterization of PRDM5 targets in relevant cancer settings is still lacking.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Prdm5 suppresses ApcMin-driven intestinal adenomas and regulates monoacylglycerol lipase expression

et al. 2013

View full text Add to dashboard Cite

PRDM proteins are tissue-specific transcription factors often deregulated in diseases, particularly in cancer where different members have been found to act as oncogenes or tumor suppressors. PRDM5 is a poorly characterized member of the PRDM family for which several studies have reported a high frequency of promoter hypermethylation in cancer types of gastrointestinal origin. We report here the characterization of Prdm5 knockout mice in the context of intestinal carcinogenesis. We demonstrate that loss of Prdm5 increases the number of adenomas throughout the murine small intestine on an Apc Min background. By using the genome-wide ChIP-seq (chromatin immunoprecipitation (ChIP) followed by DNA sequencing) and transcriptome analyses we identify loci encoding proteins involved in metabolic processes as prominent PRDM5 targets and characterize monoacylglycerol lipase (Mgll) as a direct PRDM5 target in human colon cancer cells and in Prdm5 mutant mouse intestines. Moreover, we report the downregulation of PRDM5 protein expression in human colon neoplastic lesions. In summary, our data provide the first causal link between Prdm5 loss and intestinal carcinogenesis, and uncover an extensive and novel PRDM5 target repertoire likely facilitating the tumor-suppressive functions of PRDM5.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Prdm5 Loss Increases Intestinal Adenomas Driven By Apc Mutationmentioning

confidence: 99%

Section: Mgll Is a Wnt-responsive Gene And A Functional Prdm5 Targetmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Prdm5 suppresses ApcMin-driven intestinal adenomas and regulates monoacylglycerol lipase expression

et al. 2013

View full text Add to dashboard Cite

show abstract

The Ehlers–Danlos syndromes, rare types

Brady¹,

Demirdas²,

Fournel‐Gigleux³

et al. 2017

American J of Med Genetics Pt C

187

288

View full text Add to dashboard Cite

The Ehlers–Danlos syndromes comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders, which are characterized by joint hypermobility, skin hyperextensibility, and tissue friability. In the Villefranche Nosology, six subtypes were recognized: The classical, hypermobile, vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis subtypes of EDS. Except for the hypermobile subtype, defects had been identified in fibrillar collagens or in collagen‐modifying enzymes. Since 1997, a whole spectrum of novel, clinically overlapping, rare EDS‐variants have been delineated and genetic defects have been identified in an array of other extracellular matrix genes. Advances in molecular testing have made it possible to now identify the causative mutation for many patients presenting these phenotypes. The aim of this literature review is to summarize the current knowledge on the rare EDS subtypes and highlight areas for future research. © 2017 Wiley Periodicals, Inc.

show abstract

PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression

et al. 2016

View full text Add to dashboard Cite

PRDM (PRDI‐BF1 and RIZ domain‐containing) proteins constitute a family of zinc finger proteins and play important roles in multiple cellular processes by acting as epigenetic modifiers. PRDM5 is a recently identified member of the PRDM family and may function as a tumor suppressor in several types of cancer. However, the role of PRDM5 in murine melanoma remains largely unknown. In our study, effect of PRDM5 on murine melanoma cells was determined and results showed that PRDM5 overexpression significantly promoted proliferation, migration, and invasion of murine melanoma B16F10 cells. Consistently, silencing of PRDM5 expression significantly inhibited proliferation, invasion, and migration of B16F10 cells. In vivo study also showed that PRDM5 silencing significantly inhibited the growth and metastasis of melanoma in mice. PRDM5 was then found to increase the expression and activation of JNK in B16F10 cells. JNK silencing significantly reduced PRDM5‐mediated up‐regulation of JNK expression and blocked the PRDM5‐induced proliferation and invasion of B16F10 cells. To further verify the involvement of JNK signaling in PRDM5‐induced progression of B16F10 cells, a specific JNK inhibitor was employed to inhibit the JNK signaling pathway, and results showed that PRDM5‐induced proliferation and invasion of B16F10 cells were abolished. We conclude that PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression and strategies targeting PRDM5 may be promising for the therapy of melanoma.

show abstract

Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone

Cited by 52 publications

References 39 publications

Prdm5 suppresses ApcMin-driven intestinal adenomas and regulates monoacylglycerol lipase expression

Prdm5 suppresses ApcMin-driven intestinal adenomas and regulates monoacylglycerol lipase expression

The Ehlers–Danlos syndromes, rare types

PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression

Contact Info

Product

Resources

About