@article{10902/34516,
year = {2024},
url = {https://hdl.handle.net/10902/34516},
abstract = {The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow some physical crosstalk across regulatory domains, which is at odds with the specific and precise expression of developmental genes. Here we show that developmental genes and nearby clusters of CTCF sites cooperatively foster the robust insulation of regulatory domains. By genetically dissecting a couple of representative loci in mouse embryonic stem cells, we show that CTCF sites prevent undesirable enhancer-gene contacts (i.e. physical insulation), while developmental genes preferentially contribute to regulatory insulation through non-structural mechanisms involving promoter competition rather than enhancer blocking. Overall, our work provides important insights into the insulation of regulatory domains, which in turn might help interpreting the pathological consequences of certain structural variants.},
organization = {Acknowledgements: We would like to thank all the Rada-Iglesias lab members for insightful comments and suggestions. Work in the Rada-Iglesias laboratory is supported by grant PID2021-123030NB-I00 (AR-I) funded by MCIN/AEI/ 10.13039/501100011033 and by ERDF A way of making Europe, grant RED2022-134100-T (AR-I) (REDEVNEURAL 3.0) funded by MCIN/AEI /10.13039/501100011033, grant ERC CoG PoisedLogic (862022) (A.R.-I.) funded by the European Research Council, grant ENHPATHY H2020-MSCA-ITN-2019-860002 (A.R.-I.) funded by the European Commission, grant Chrom_rare HORIZON-MSCA-2021-DN-01-101073334 (A.R.-I.) funded by the European Commission. E.M.B was granted with a fellowship from the network PIE-202120E047-Conexiones-Life.},
publisher = {Nature Publishing Group},
publisher = {Nature Communications, 2024, 15, 7258},
title = {Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition},
author = {Ealo Rodríguez, Thais and Sánchez Gaya, Víctor and Respuela Alonso, Patricia and Muñoz San Martín, María and Martín-Batista, Elva and Haro Gabicagogeascoa, Endika and Rada Iglesias, Álvaro},
}