Recently Evolved Enhancers Emerge with High Interindividual Variability and Less Frequently Associate with Disease

TY - JOUR

T1 - Recently Evolved Enhancers Emerge with High Interindividual Variability and Less Frequently Associate with Disease

AU - Castelijns, Bas

AU - Baak, Mirna L

AU - Geeven, Geert

AU - Vermunt, Marit W

AU - Wiggers, Caroline R M

AU - Timpanaro, Ilia S

AU - Kondova, Ivanela

AU - de Laat, Wouter

AU - Creyghton, Menno P

N1 - Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2020/6/23

Y1 - 2020/6/23

N2 - Mutations in non-coding regulatory DNA such as enhancers underlie a wide variety of diseases including developmental disorders and cancer. As enhancers rapidly evolve, understanding their function and configuration in non-human disease models can have important clinical applications. Here, we analyze enhancer configurations in tissues isolated from the common marmoset, a widely used primate model for human disease. Integrating these data with human and mouse data, we find that enhancers containing trait-associated variants are preferentially conserved. In contrast, most human-specific enhancers are highly variable between individuals, with a subset failing to contact promoters. These are located further away from genes and more often reside in inactive B-compartments. Our data show that enhancers typically emerge as instable elements with minimal biological impact prior to their integration in a transcriptional program. Furthermore, our data provide insight into which trait variations in enhancers can be faithfully modeled using the common marmoset.

AB - Mutations in non-coding regulatory DNA such as enhancers underlie a wide variety of diseases including developmental disorders and cancer. As enhancers rapidly evolve, understanding their function and configuration in non-human disease models can have important clinical applications. Here, we analyze enhancer configurations in tissues isolated from the common marmoset, a widely used primate model for human disease. Integrating these data with human and mouse data, we find that enhancers containing trait-associated variants are preferentially conserved. In contrast, most human-specific enhancers are highly variable between individuals, with a subset failing to contact promoters. These are located further away from genes and more often reside in inactive B-compartments. Our data show that enhancers typically emerge as instable elements with minimal biological impact prior to their integration in a transcriptional program. Furthermore, our data provide insight into which trait variations in enhancers can be faithfully modeled using the common marmoset.

U2 - 10.1016/j.celrep.2020.107799

DO - 10.1016/j.celrep.2020.107799

M3 - Article

C2 - 32579926

SN - 2211-1247

VL - 31

SP - 107799

JO - Cell Reports

JF - Cell Reports

IS - 12

ER -