Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/52428
Título: AID stabilizes stem-cell phenotype by removing epigenetic memory of pluripotency genes
Autores/as: Kumar, Ritu
Dimenna, Lauren
Schrode, Nadine
Liu, Ting Chun
Franck, Philipp
Muñoz-Descalzo, Silvia 
Hadjantonakis, Anna Katerina
Zarrin, Ali A.
Chaudhuri, Jayanta
Elemento, Olivier
Evans, Todd
Clasificación UNESCO: 32 Ciencias médicas
310903 Inmunología
Palabras clave: Epigenetic memory
Induced pluripotent stem cells
Pluripotency
Reprogramming
Fecha de publicación: 2013
Publicación seriada: Nature 
Resumen: The activation-induced cytidine deaminase (AID; also known as AICDA) enzyme is required for somatic hypermutation and class switch recombination at the immunoglobulin locus. In germinal-centre B cells, AID is highly expressed, and has an inherent mutator activity that helps generate antibody diversity. However, AID may also regulate gene expression epigenetically by directly deaminating 5-methylcytosine in concert with base-excision repair to exchange cytosine. This pathway promotes gene demethylation, thereby removing epigenetic memory. For example, AID promotes active demethylation of the genome in primordial germ cells. However, different studies have suggested either a requirement or a lack of function6 for AID in promoting pluripotency in somatic nuclei after fusion with embryonic stem cells. Here we tested directly whether AID regulates epigenetic memory by comparing the relative ability of cells lacking AID to reprogram from a differentiated murine cell type to an induced pluripotent stem cell. We show that Aid-null cells are transiently hyper-responsive to the reprogramming process. Although they initiate expression of pluripotency genes, they fail to stabilize in the pluripotent state. The genome of Aid-null cells remains hypermethylated in reprogramming cells, and hypermethylated genes associated with pluripotency fail to be stably upregulated, including many MYC target genes. Recent studies identified a late step of reprogramming associated with methylation status, and implicated a secondary set of pluripotency network components. AID regulates this late step, removing epigenetic memory to stabilize the pluripotent state.
URI: http://hdl.handle.net/10553/52428
ISSN: 0028-0836
DOI: 10.1038/nature12299
Fuente: Nature[ISSN 0028-0836],v. 500, p. 89-92
Colección:Artículos
Vista completa

Citas SCOPUSTM   

79
actualizado el 24-mar-2024

Visitas

55
actualizado el 17-feb-2024

Google ScholarTM

Verifica

Altmetric


Comparte



Exporta metadatos



Los elementos en ULPGC accedaCRIS están protegidos por derechos de autor con todos los derechos reservados, a menos que se indique lo contrario.