Evidence map›Paper›PMID 27058665›Full record

ArticleCell2016

Suppression of Enhancer Overactivation by a RACK7-Histone Demethylase Complex.

Hongjie Shen, Wenqi Xu, Rui Guo, Bowen Rong, Lei Gu, Zhentian Wang, Chenxi He, Lijuan Zheng, Xin Hu, Zhen Hu and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 187 citations in OpenAlex.

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72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 2 countries.

Hongjie ShenKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China.
Wenqi XuKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China.
Rui GuoKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Bowen RongKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Lei GuNewborn Medicine Division, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Zhentian WangKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Chenxi HeKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Lijuan ZhengKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Xin HuKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Zhen HuKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Zhi-Ming ShaoKey Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Pengyuan YangDepartment of System Biology, Institutes of Biomedical Sciences, Fudan University, 138 Yixue Yuan Road, Shanghai 200032, China.
Feizhen WuKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Yujiang Geno ShiKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China; Division of Endocrinology, Brigham and Women Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yang ShiKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China; Newborn Medicine Division, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: yshi@hms.harvard.edu.
Fei LanKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Key Laboratory of Epigenetics, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China. Electronic address: fei_lan@fudan.edu.cn.
Fudan University · CNChildren's Hospital of Fudan University · CNFudan University Shanghai Cancer Center · CNBoston Children's Hospital · USHarvard University · US

Funding

Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI POMEROY, SCOTT LOREN · 2016 to 2020
$5.2M
Histone Demethylases and Regulation of Chromatin and Transcription in EukaryotesR01CA118487 · NCI · HARVARD MEDICAL SCHOOL · PI SHI, YANG · 2006 to 2017
$3.6M
NCI NIH HHS CA118487NCI NIH HHS R01 CA118487NICHD NIH HHS U54 HD090255
6 · The paper itself

Abstract

Regulation of enhancer activity is important for controlling gene expression programs. Here, we report that a biochemical complex containing a potential chromatin reader, RACK7, and the histone lysine 4 tri-methyl (H3K4me3)-specific demethylase KDM5C occupies many active enhancers, including almost all super-enhancers. Loss of RACK7 or KDM5C results in overactivation of enhancers, characterized by the deposition of H3K4me3 and H3K27Ac, together with increased transcription of eRNAs and nearby genes. Furthermore, loss of RACK7 or KDM5C leads to de-repression of S100A oncogenes and various cancer-related phenotypes. Our findings reveal a RACK7/KDM5C-regulated, dynamic interchange between histone H3K4me1 and H3K4me3 at active enhancers, representing an additional layer of regulation of enhancer activity. We propose that RACK7/KDM5C functions as an enhancer "brake" to ensure appropriate enhancer activity, which, when compromised, could contribute to tumorigenesis.

Indexed as

CarcinogenesisEnhancer Elements, GeneticGene Expression RegulationAnimalsGene Knockout TechniquesHeterograftsHistone DemethylasesHumansMiceNeoplasm TransplantationReceptors, Cell SurfaceReceptors for Activated C KinaseS100 ProteinsTranscription, GeneticHistone DemethylasesKDM5C protein, humanReceptors, Cell SurfaceReceptors for Activated C KinaseS100 Proteins

Identifiers

PMID27058665
PMCPMC4826479
OpenAlexW2313634983

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.