Literature search services are currently unavailable. During our hosting provider's UPS upgrade we experienced a hardware failure and are currently working to resolve the issue.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development.

Charged multivesicular body protein 1A (CHMP1A; also known as chromatin-modifying protein 1A) is a member of the ESCRT-III (endosomal sorting complex required for transport-III) complex but is also suggested to localize to the nuclear matrix and regulate chromatin structure. Here, we show that loss-of-function mutations in human CHMP1A cause reduced cerebellar size (pontocerebellar hypoplasia) and reduced cerebral cortical size (microcephaly). CHMP1A-mutant cells show impaired proliferation, with increased expression of INK4A, a negative regulator of stem cell proliferation. Chromatin immunoprecipitation suggests loss of the normal INK4A repression by BMI in these cells. Morpholino-based knockdown of zebrafish chmp1a resulted in brain defects resembling those seen after bmi1a and bmi1b knockdown, which were partially rescued by INK4A ortholog knockdown, further supporting links between CHMP1A and BMI1-mediated regulation of INK4A. Our results suggest that CHMP1A serves as a critical link between cytoplasmic signals and BMI1-mediated chromatin modifications that regulate proliferation of central nervous system progenitor cells.

Pubmed ID: 23023333


  • Mochida GH
  • Ganesh VS
  • de Michelena MI
  • Dias H
  • Atabay KD
  • Kathrein KL
  • Huang HT
  • Hill RS
  • Felie JM
  • Rakiec D
  • Gleason D
  • Hill AD
  • Malik AN
  • Barry BJ
  • Partlow JN
  • Tan WH
  • Glader LJ
  • Barkovich AJ
  • Dobyns WB
  • Zon LI
  • Walsh CA


Nature genetics

Publication Data

November 29, 2012

Associated Grants

  • Agency: NINDS NIH HHS, Id: R01 NS035129
  • Agency: NINDS NIH HHS, Id: R01NS035129
  • Agency: FIC NIH HHS, Id: R21 TW008223
  • Agency: FIC NIH HHS, Id: R21TW008223
  • Agency: NIGMS NIH HHS, Id: T32 GM007753
  • Agency: NIMH NIH HHS, Id: T32 MH020017

Mesh Terms

  • Animals
  • Cell Proliferation
  • Cerebellar Cortex
  • Cyclin-Dependent Kinase Inhibitor p16
  • Endosomal Sorting Complexes Required for Transport
  • Gene Expression Regulation, Developmental
  • Genetic Linkage
  • HEK293 Cells
  • Humans
  • Mice
  • Microcephaly
  • Mitogen-Activated Protein Kinase 7
  • Mutation
  • NIH 3T3 Cells
  • Neural Stem Cells
  • Neurons
  • Polymorphism, Single Nucleotide
  • Zebrafish