The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27 Kip1 and p18 INK4c
Open accessAbstract
Menin, the product of the Men1 gene mutated in familial multiple endocrine neoplasia type 1 (MEN1), regulates transcription in differentiated cells. Menin associates with and modulates the histone methyltransferase activity of a nuclear protein complex to activate gene expression. However, menin-dependent histone methyltransferase activity in endocrine cells has not been demonstrated, and the mechanism of endocrine tumor suppression by menin remains unclear. Here, we show that menin-dependent histone methylation maintains the in vivo expression of cyclin-dependent kinase (CDK) inhibitors to prevent pancreatic islet tumors. In vivo expression of CDK inhibitors, including p27 and p18, and other cell cycle regulators is disrupted in mouse islet tumors lacking menin. Chromatin immunoprecipitation studies reveal that menin directly associates with regions of the p27 and p18 promoters and increases methylation of lysine 4 (Lys-4) in histone H3 associated with these promoters. Moreover, H3 Lys-4 methylation associated with p27 and p18 is reduced in islet tumors from Men1 mutant mice. Thus, H3 Lys-4 methylation is a crucial function of menin in islet tumor suppression. These studies suggest an epigenetic mechanism of tumor suppression: by promoting histone modifications, menin maintains transcription at multiple loci encoding cell cycle regulators essential for endocrine growth control.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756
Chen, X., Xiu, M., Xing, J., Yu, S., Min, D., & Guo, F. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479439 · Cited by 5,742
Positional Cloning of the Gene for Multiple Endocrine Neoplasia-Type 1
Chandrasekharappa, S. C., Guru, S. C., Manickam, P., Olufemi, S.-E., Collins, F. S., Emmert-Buck, M. R., Debelenko, L. V., Zhuang, Z., Lubensky, I. A., Liotta, L. A., et al. (1997) · Science · doi:10.1126/science.276.5311.404 · Cited by 2,082
Nakayama, K., Ishida, N., Shirane, M., Inomata, A., Inoue, T., Shishido, N., Horii, I., Loh, D. Y., & Nakayama, K.-I. (1996) · Cell · doi:10.1016/s0092-8674(00)81237-4 · Cited by 1,547
Fero, M. L., Rivkin, M., Tasch, M., Porter, P., Carow, C. E., Firpo, E., Polyak, K., Tsai, L.-H., Broudy, V., Perlmutter, R. M., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81239-8 · Cited by 1,457
AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
Medema, R. H., Kops, G. J. P. L., Bos, J. L., & Burgering, B. M. T. (2000) · Nature · doi:10.1038/35008115 · Cited by 1,438
MIYAZAKI, J.-I., ARAKI, K., YAMATO, E., IKEGAMI, H., ASANO, T., SHIBASAKI, Y., OKA, Y., & YAMAMURA, K.-I. (1990) · Endocrinology · doi:10.1210/endo-127-1-126 · Cited by 1,266
Enhanced Growth of Mice Lacking the Cyclin-Dependent Kinase Inhibitor Function of p27
Kiyokawa, H., Kineman, R. D., Manova-Todorova, K. O., Soares, V. C., Hoffman, E. S., Ono, M., Khanam, D., Hayday, A. C., Frohman, L. A., & Koff, A. (1996) · Cell · doi:10.1016/s0092-8674(00)81238-6 · Cited by 1,251
Epigenetic Regulation of Cellular Memory by the Polycomb and Trithorax Group Proteins
Ringrose, L., & Paro, R. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.38.072902.091907 · Cited by 1,077
MLL Targets SET Domain Methyltransferase Activity to Hox Gene Promoters
Milne, T. A., Briggs, S. D., Brock, H. W., Martin, M. E., Gibbs, D., Allis, C. D., & Hess, J. L. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00741-4 · Cited by 1,053
Cited by
The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy
Chu, I. M., Hengst, L., & Slingerland, J. M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2347 · Cited by 990
Lemos, M. C., & Thakker, R. V. (2008) · Human Mutation · doi:10.1002/humu.20605 · Cited by 675
Menin Critically Links MLL Proteins with LEDGF on Cancer-Associated Target Genes
Yokoyama, A., & Cleary, M. L. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.003 · Cited by 555
Jensen, R. T., Berna, M. J., Bingham, D. B., & Norton, J. A. (2008) · Cancer · doi:10.1002/cncr.23648 · Cited by 488
Calcineurin/NFAT signalling regulates pancreatic β-cell growth and function
Heit, J. J., Apelqvist, Å. A., Gu, X., Winslow, M. M., Neilson, J. R., Crabtree, G. R., & Kim, S. K. (2006) · Nature · doi:10.1038/nature05097 · Cited by 444
Self-citation
Metadata
- Authors
- Karnik, S. K., Hughes, C. M., Gu, X., Rozenblatt-Rosen, O., McLean, G. W., Xiong, Y., Meyerson, M., & Kim, S. K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-09-29
- Volume
- 102
- Issue
- 41
- Pages
- 14659-14664
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2124584525
- Cited by
- 403
- References
- 38
- FWCI
- 17.23
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27 Kip1 and p18 INK4c. https://app.cochat.ai/papers/10.1073/pnas.0503484102
- The paper
- Karnik, S. K., Hughes, C. M., Gu, X., Rozenblatt-Rosen, O., McLean, G. W., Xiong, Y., Meyerson, M., & Kim, S. K. (2005). Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27 Kip1 and p18 INK4c. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0503484102
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
