Published May 10, 2024
| Version v1
Journal article
Open
Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression
Creators
- 1. Centro Andaluz de Biología del Desarrollo
- 2. Centro Nacional de Investigaciones Cardiovasculares
- 3. Centro Nacional de Investigaciones Oncológicas
- 4. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares
- 5. University of Cologne
- 6. University of Cantabria
- 7. University of Chicago
Description
MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.
Data availability
The Raw data generated in this study have been deposited in the Figshare database and are available from https://doi.org/10.6084/m9.figshare.24794559. The data for some images that were not quantified but only qualitatively analyzed and were too large for the allowance in the Figshare repository can be obtained from M.T. upon request. Sequencing data generated in this study are available from the GEO database with accession number GSE222299. The ChIPseq data used in this study are publicly available from the ChIPseq Atlas (https://chip-atlas.org/peak) and the PLAC-seq data used in this study are available from the 3D genome database (http://3dgenome.fsm.northwestern.edu/). Source data are provided with this paper.Files
Regulation-of-Myc-transcription-by-an-enhancer-cluster-dedicated-to-pluripotency-and-early-embryonic-expression.pdf
Additional details
Identifiers
- DOI
- 10.1038/s41467-024-48258-5
- Other
- oai:uchicago.tind.io:11792
Funding
- Agencia Estatal de Investigación
- PGC2018-096486-B-I00
- Agencia Estatal de Investigación
- PID2022-140058NB-C31
- European Commission
- H2020 Program
- Comunidad de Madrid
- P2022/BMD-7245 CARDIOBOOST-CM