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Literature DB >> 19390085

Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation.

Sangeeta Dhawan¹, Shuen-Ing Tschen, Anil Bhushan.

Abstract

The molecular mechanisms that regulate the age-induced increase of p16(INK4a) expression associated with decreased beta-cell proliferation and regeneration are not well understood. We report that in aged islets, derepression of the Ink4a/Arf locus is associated with decreased Bmi-1 binding, loss of H2A ubiquitylation, increased MLL1 recruitment, and a concomitant increase in H3K4 trimethylation. During beta-cell regeneration these histone modifications are reversed resulting in reduced p16(INK4a) expression and increased proliferation. We suggest that PcG and TrxG proteins impart a combinatorial code of histone modifications on the Ink4a/Arf locus to control beta-cell proliferation during aging and regeneration.

Entities: Disease Gene

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Year: 2009 PMID： 19390085 PMCID： PMC2675870 DOI： 10.1101/gad.1742609

Source DB: PubMed Journal: Genes Dev ISSN： 0890-9369 Impact factor: 11.361

25 in total

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Journal: Nature Date: 2003-10-22 Impact factor: 49.962

2. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.

Authors: Yuval Dor; Juliana Brown; Olga I Martinez; Douglas A Melton
Journal: Nature Date: 2004-05-06 Impact factor: 49.962

3. Role of histone H2A ubiquitination in Polycomb silencing.

Authors: Hengbin Wang; Liangjun Wang; Hediye Erdjument-Bromage; Miguel Vidal; Paul Tempst; Richard S Jones; Yi Zhang
Journal: Nature Date: 2004-09-22 Impact factor: 49.962

4. Mammalian Trithorax and polycomb-group homologues are antagonistic regulators of homeotic development.

Authors: R D Hanson; J L Hess; B D Yu; P Ernst; M van Lohuizen; A Berns; N M van der Lugt; C S Shashikant; F H Ruddle; M Seto; S J Korsmeyer
Journal: Proc Natl Acad Sci U S A Date: 1999-12-07 Impact factor: 11.205

5. Immunohistochemical survey of p16INK4A expression in normal human adult and infant tissues.

Authors: G P Nielsen; A O Stemmer-Rachamimov; J Shaw; J E Roy; J Koh; D N Louis
Journal: Lab Invest Date: 1999-09 Impact factor: 5.662

6. Ink4a/Arf expression is a biomarker of aging.

Authors: Janakiraman Krishnamurthy; Chad Torrice; Matthew R Ramsey; Grigoriy I Kovalev; Khalid Al-Regaiey; Lishan Su; Norman E Sharpless
Journal: J Clin Invest Date: 2004-11 Impact factor: 14.808

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8. PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance.

Authors: Rohit N Kulkarni; Ulupi S Jhala; Jonathon N Winnay; Stan Krajewski; Marc Montminy; C Ronald Kahn
Journal: J Clin Invest Date: 2004-09 Impact factor: 14.808

9. Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene.

Authors: N M van der Lugt; J Domen; K Linders; M van Roon; E Robanus-Maandag; H te Riele; M van der Valk; J Deschamps; M Sofroniew; M van Lohuizen
Journal: Genes Dev Date: 1994-04-01 Impact factor: 11.361

10. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus.

Authors: J J Jacobs; K Kieboom; S Marino; R A DePinho; M van Lohuizen
Journal: Nature Date: 1999-01-14 Impact factor: 49.962

131 in total

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Authors: Jennifer L Plank; Audrey Y Frist; Alison W LeGrone; Mark A Magnuson; Patricia A Labosky
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Authors: Sangeeta Dhawan; Senta Georgia; Shuen-Ing Tschen; Guoping Fan; Anil Bhushan
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Review 3. Epigenetic cancer prevention mechanisms in skin cancer.

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Journal: AAPS J Date: 2013-08-01 Impact factor: 4.009

4. Tissue-specific p19Arf regulation dictates the response to oncogenic K-ras.

Authors: Nathan P Young; Tyler Jacks
Journal: Proc Natl Acad Sci U S A Date: 2010-05-17 Impact factor: 11.205

5. Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism.

Authors: Filip Bednar; Heather K Schofield; Meredith A Collins; Wei Yan; Yaqing Zhang; Nikhil Shyam; Jaime A Eberle; Luciana L Almada; Kenneth P Olive; Nabeel Bardeesy; Martin E Fernandez-Zapico; Daisuke Nakada; Diane M Simeone; Sean J Morrison; Marina Pasca di Magliano
Journal: Carcinogenesis Date: 2015-05-04 Impact factor: 4.944