Dynamics of chromatin marks and the role of JMJD3 during pancreatic endocrine cell fate commitment.
Development
; 145(6)2018 03 20.
Article
em En
| MEDLINE
| ID: mdl-29559448
ABSTRACT
Pancreatic endocrine lineages are derived from pancreatic progenitors that undergo a cell fate transition requiring a switch from low to high Ngn3 expression. However, the underlying chromatin regulatory mechanisms are unclear. Here, we performed epigenomic analysis of gene regulatory loci featuring histone marks in cells with low or high level of Ngn3 expression. In combination with transcriptomic analysis, we discovered that in Ngn3-high cells, the removal of H3K27me3 was associated with the activation of key transcription factors and the establishment of primed and active enhancers. Deletion of Jmjd3, a histone demethylase for H3K27me3, at the pancreatic progenitor stage impaired the efficiency of endocrine cell fate transition and thereafter islet formation. Curiously, single-cell RNA-seq revealed that the transcriptome and developmental pathway of Ngn3-high cells were not affected by the deletion of Jmjd3 Our study indicates sequential chromatin events and identifies a crucial role for Jmjd3 in regulating the efficiency of the transition from Ngn3-low to Ngn3-high cells.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pâncreas
/
Cromatina
/
Histonas
/
Células Endócrinas
/
Histona Desmetilases com o Domínio Jumonji
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Development
Assunto da revista:
BIOLOGIA
/
EMBRIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China