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Chromatin remodeling effects on enhancer activity

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Abstract

During organism development, a diversity of cell types emerges with disparate, yet stable profiles of gene expression with distinctive cellular functions. In addition to gene promoters, the genome contains enhancer regulatory sequences, which are implicated in cellular specialization by facilitating cell-type and tissue-specific gene expression. Enhancers are DNA binding elements characterized by highly sophisticated and various mechanisms of action allowing for the specific interaction of general and tissue-specific transcription factors (TFs). However, eukaryotic organisms package their genetic material into chromatin, generating a physical barrier for TFs to interact with their cognate sequences. The ability of TFs to bind DNA regulatory elements is also modulated by changes in the chromatin structure, including histone modifications, histone variants, ATP-dependent chromatin remodeling, and the methylation status of DNA. Furthermore, it has recently been revealed that enhancer sequences are also transcribed into a set of enhancer RNAs with regulatory potential. These interdependent processes act in the context of a complex network of chromatin interactions, which together contributes to a renewed vision of how gene activation is coordinated in a cell-type-dependent manner. In this review, we describe the interplay between genetic and epigenetic aspects associated with enhancers and discuss their possible roles on enhancer function.

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Acknowledgments

We acknowledge Karin Meier for critical reading of the manuscript. This work was supported by the DGAPA-PAPIIT, UNAM (IN209403, IN203811 and IN201114), CONACyT (42653-Q, 128464 and 220503) and Fronteras de la Ciencia-2015 (Grant 290) to FR-T, and by a PhD fellowship from CONACyT and Programa de Apoyo a los Estudios del Posgrado (PAEP), UNAM to EG-G and RA-M. Additional support was provided by the Ph.D. Graduate Program, “Doctorado en Ciencias Bioquímicas y Biomédicas”, to the Instituto de Fisiología Celular, Universidad Nacional Autónoma de México.

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  1. Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, C.P. 04510, Mexico City, México

    Estela García-González, Rodrigo Arzate-Mejía & Félix Recillas-Targa

  2. Department of Biochemistry and Molecular Biophysics, Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York City, NY, 10027, USA

    Martín Escamilla-Del-Arenal

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  1. Estela García-González
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Correspondence to Félix Recillas-Targa.

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García-González, E., Escamilla-Del-Arenal, M., Arzate-Mejía, R. et al. Chromatin remodeling effects on enhancer activity. Cell. Mol. Life Sci. 73, 2897–2910 (2016). https://doi.org/10.1007/s00018-016-2184-3

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