Identification and Functional Validation of Super-enhancers in

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Nov 21

PMID 36409894

Authors

Hainan Zhao

Mingyu Yang

Jade Bishop

Yuhan Teng

Yingxue Cao

Brandon D Beall

Shuanglin Li

Tongxin Liu

Qingxi Fang

Chao Fang

Haoyang Xin

Hans-Wilhelm Nutzmann

Anne Osbourn

Fanli Meng

Jiming Jiang

Affiliations

Soon will be listed here.

Abstract

Super-enhancers (SEs) are exceptionally large enhancers and are recognized to play prominent roles in cell identity in mammalian species. We surveyed the genomic regions containing large clusters of accessible chromatin regions (ACRs) marked by deoxyribonuclease (DNase) I hypersensitivity in . We identified a set of 749 putative SEs, which have a minimum length of 1.5 kilobases and represent the top 2.5% of the largest ACR clusters. We demonstrate that the genomic regions associating with these SEs were more sensitive to DNase I than other nonpromoter ACRs. The SEs were preferentially associated with topologically associating domains. Furthermore, the SEs and their predicted cognate genes were frequently associated with organ development and tissue identity in . Therefore, the SEs and their cognate genes mirror the functional characteristics of those reported in mammalian species We developed CRISPR/Cas-mediated deletion lines of a 3,578-bp SE associated with the thalianol biosynthetic gene cluster (BGC). Small deletions (131-157 bp) within the SE resulted in distinct phenotypic changes and transcriptional repression of all five thalianol genes. In addition, T-DNA insertions in the SE region resulted in transcriptional alteration of all five thalianol genes. Thus, this SE appears to play a central role in coordinating the operon-like expression pattern of the thalianol BGC.

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