CDK-Mediator and FBXL19 prime developmental genes for activation by promoting atypical regulatory interactions.
Acetylation
Animals
Cell Differentiation
/ genetics
Cyclin-Dependent Kinase 8
/ metabolism
DNA-Binding Proteins
/ genetics
F-Box Proteins
/ genetics
Gene Expression Regulation, Developmental
Genes, Developmental
Histones
/ metabolism
Lysine
/ metabolism
Mice
Mouse Embryonic Stem Cells
/ metabolism
Promoter Regions, Genetic
Protein Binding
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
06 04 2020
06 04 2020
Historique:
accepted:
21
01
2020
revised:
20
01
2020
received:
03
10
2019
pubmed:
31
1
2020
medline:
21
5
2020
entrez:
31
1
2020
Statut:
ppublish
Résumé
Appropriate developmental gene regulation relies on the capacity of gene promoters to integrate inputs from distal regulatory elements, yet how this is achieved remains poorly understood. In embryonic stem cells (ESCs), a subset of silent developmental gene promoters are primed for activation by FBXL19, a CpG island binding protein, through its capacity to recruit CDK-Mediator. How mechanistically these proteins function together to prime genes for activation during differentiation is unknown. Here we discover that in mouse ESCs FBXL19 and CDK-Mediator support long-range interactions between silent gene promoters that rely on FBXL19 for their induction during differentiation and gene regulatory elements. During gene induction, these distal regulatory elements behave in an atypical manner, in that the majority do not acquire histone H3 lysine 27 acetylation and no longer interact with their target gene promoter following gene activation. Despite these atypical features, we demonstrate by targeted deletions that these distal elements are required for appropriate gene induction during differentiation. Together these discoveries demonstrate that CpG-island associated gene promoters can prime genes for activation by communicating with atypical distal gene regulatory elements to achieve appropriate gene expression.
Identifiants
pubmed: 31996894
pii: 5717747
doi: 10.1093/nar/gkaa064
pmc: PMC7102981
doi:
Substances chimiques
DNA-Binding Proteins
0
F-Box Proteins
0
FBXL19 protein, mouse
0
Histones
0
Cdk8 protein, mouse
EC 2.7.11.22
Cyclin-Dependent Kinase 8
EC 2.7.11.22
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2942-2955Subventions
Organisme : Wellcome Trust
ID : 110286/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 209400/Z/17/Z
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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