Enhancers and promoters are the most important two types of gene expression regulatory elements in higher animals, especially humans
Nature This study proposed an enhancer-selected promoter model called enhancer release and retargeting (ERR)
High-resolution chromatin structure data show that enhancers and promoters often form small-scale loops, generally 10-50Kb apart [1, 2]
In order to understand the enhancer-promoter pairing selection mechanism, based on the chromosome conformation capture technology 4C-seq and ChIA-PET data, the authors selected 4 pairs of enhancer-promoter to study their relationship
Figure 1.
Figure 1.
Figure 2.
Figure 2.
Furthermore, the authors found that among other genes adjacent to TFF1, the TFF3 promoter also has a CTCF site, but its binding is weaker than the CTCF of the TFF1 promoter, but stronger than the other two genes
Figure 3.
Figure 3.
Figure 4.
Figure 4.
Figure 5.
Figure 5.
The significance of this work is twofold
.
First, the authors provide new mechanistic evidence to understand and describe the process of enhancer-promoter interaction
.
These mechanisms reveal the specific or deformable source of enhancer-promoter selection, and provide new ideas to further study the role of this important process in normal development and gene expression regulation
.
Second, this work shows that many DNA sequences within the chromosomal interaction domain or topological domain (TAD), rather than at the edge of the domain, play an important role in determining enhancer-promoter pairing
.
These findings reveal that many disease-related (such as cancer and Parkinson's disease) single nucleotide variants or small sequence deletions are likely to affect the expression of disease-related genes through the mechanism of ERR
.
Postdoctoral fellows Wu Xiuhuan (Korea), Dr.
Shao Jiaofang (currently returning to work at Nanjing Medical University), and Dr.
Xiongfeng are the main authors
.
The Zhang Zhengdong group of Albert Einstein College of Medicine in New York and the postdoc Joydeep Mitra made important contributions to this work
.
(Source: Science Net)
There are currently two postdoctoral vacancies in the Li Wenbo teacher group
.
Students who are interested in epigenetic regulation (especially enhancers, three-dimensional genomes and non-coding RNA) are welcome to join .
Please contact Mr.
Li directly at wenbo.
li@uth.
tmc.
edu
.
Related paper information: https://doi.
org/10.
1038/s41586-021-03577-1
https://doi.
org/10.
1038/s41586-021-03577-1 references:
1.
Hsieh TS, Cattoglio C, Slobodyanyuk E, Hansen AS, Rando OJ, Tjian R, Darzacq X: Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding.
Mol Cell 2020, 78(3):539-553 e538.
2.
Schoenfelder S, Fraser P: Long-range enhancer-promoter contacts in gene expression control.
Nat Rev Genet 2019, 20(8):437-455.
3.
Gasperini M, Hill AJ, McFaline-Figueroa JL, Martin B, Kim S, Zhang MD, Jackson D, Leith A, Schreiber J, Noble WS et al: A Genome-wide Framework for Mapping Gene Regulation via Cellular Genetic Screens.
Cell 2019, 176(6):1516.
4.
van Arensbergen J, van Steensel B, Bussemaker HJ: In search of the determinants of enhancer-promoter interaction specificity.
Trends Cell Biol 2014, 24(11):695-702.
5.
Li W, Notani D, Rosenfeld MG: Enhancers as non-coding RNA transcription units: recent insights and future perspectives.
Nat Rev Genet 2016, 17(4):207-223.
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