Cis-Regulatory Elements in Mammals

Abstract

In cis-regulatory elements, enhancers and promoters with complex molecular interactions are used to coordinate gene transcription through physical proximity and chemical modifications. These processes subsequently influence the phenotypic characteristics of an organism. An in-depth exploration of enhancers and promoters can substantially enhance our understanding of gene regulatory networks, shedding new light on mammalian development, evolution and disease pathways. In this review, we provide a comprehensive overview of the intrinsic structural attributes, detection methodologies as well as the operational mechanisms of enhancers and promoters, coupled with the relevant novel and innovative investigative techniques used to explore their actions. We further elucidated the state-of-the-art research on the roles of enhancers and promoters in the realms of mammalian development, evolution and disease, and we conclude with forward-looking insights into prospective research avenues.

Keywords: cis-regulatory elements; enhancers; mammals; promoters.

Figure 1

Schematic diagram of enhancer structure. Abbreviations: H3K27ac, acetylation of lysine 27 on histone 3; H3K4me1, monomethylation on lysine 4 of histone H3; TF, transcription factor; GTF, general transcription factor; Pol II, RNA polymerase II; Co, cofactor. The black line indicates DNA.

Figure 2

Schematic diagram of promoter structure. Abbreviations: H3K27ac, acetylation of lysine 27 on histone 3; H3K4me3, Trimethylation of histone H3 lysine 4. TF, transcription factor; GTF, general transcription factor; Pol II, RNA polymerase II; PIC, pre-initiation complex; BRE^u, BRE upstream (of TATA box); BRE^d, BRE downstream (of TATA box); Inr, initiator element; DPE, downstream promoter element. The black line indicates DNA.

Figure 3

A summary diagram of the techniques used for studying the EP interactions.

Figure 4

Schematic diagram of the chromatin loop structure. (A) Morphological diagram of chromatin in the nucleus. (B) A TAD structure diagram. Abbreviations: TAD, topologically associated structural domains; Cohesin, adhesion protein; CTCF, CCCTC-binding factor. (C) A TAD contact matrix diagram. (D) Diagram of the loop structure. Abbreviations: TF, transcription factor; YY1, transcription factor Yin Yang 1; Co, cofactor. Gray lines indicate DNA.