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Mechanisms of Enhancer Action: the Known and the Unknown

Overview
Journal Genome Biol
Specialties Biology
Genetics
Date 2021 Apr 16
PMID 33858480
Citations 141
Authors
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Abstract

Differential gene expression mechanisms ensure cellular differentiation and plasticity to shape ontogenetic and phylogenetic diversity of cell types. A key regulator of differential gene expression programs are the enhancers, the gene-distal cis-regulatory sequences that govern spatiotemporal and quantitative expression dynamics of target genes. Enhancers are widely believed to physically contact the target promoters to effect transcriptional activation. However, our understanding of the full complement of regulatory proteins and the definitive mechanics of enhancer action is incomplete. Here, we review recent findings to present some emerging concepts on enhancer action and also outline a set of outstanding questions.

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References
1.
Stossi F, Dandekar R, Mancini M, Gu G, Fuqua S, Nardone A . Estrogen-induced transcription at individual alleles is independent of receptor level and active conformation but can be modulated by coactivators activity. Nucleic Acids Res. 2020; 48(4):1800-1810. PMC: 7039002. DOI: 10.1093/nar/gkz1172. View

2.
Tsai M, OMalley B . Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem. 1994; 63:451-86. DOI: 10.1146/annurev.bi.63.070194.002315. View

3.
Hadjur S, Williams L, Ryan N, Cobb B, Sexton T, Fraser P . Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus. Nature. 2009; 460(7253):410-3. PMC: 2869028. DOI: 10.1038/nature08079. View

4.
Nepal C, Taranta A, Hadzhiev Y, Pundhir S, Mydel P, Lenhard B . Ancestrally Duplicated Conserved Noncoding Element Suggests Dual Regulatory Roles of HOTAIR in cis and trans. iScience. 2020; 23(4):101008. PMC: 7139118. DOI: 10.1016/j.isci.2020.101008. View

5.
Chen Y, Bates D, Dey R, Chen P, Dantas Machado A, Laird-Offringa I . DNA binding by GATA transcription factor suggests mechanisms of DNA looping and long-range gene regulation. Cell Rep. 2012; 2(5):1197-206. PMC: 3978094. DOI: 10.1016/j.celrep.2012.10.012. View