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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Structural insight into autoinhibition and histone H3-induced activation of DNMT3A
|
|---|---|
| Published in |
Nature, November 2014
|
| DOI | 10.1038/nature13899 |
| Pubmed ID | |
| Authors |
Xue Guo, Ling Wang, Jie Li, Zhanyu Ding, Jianxiong Xiao, Xiaotong Yin, Shuang He, Pan Shi, Liping Dong, Guohong Li, Changlin Tian, Jiawei Wang, Yao Cong, Yanhui Xu |
| Abstract |
DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B, and the methylation patterns vary with developmental stages and cell types. DNA methyltransferase 3-like protein (DNMT3L) is a catalytically inactive paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a. Recent studies have established a connection between DNA methylation and histone modifications, and revealed a histone-guided mechanism for the establishment of DNA methylation. The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes unmethylated histone H3 (H3K4me0). The histone H3 tail stimulates the enzymatic activity of Dnmt3a in vitro, whereas the molecular mechanism remains elusive. Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3 tail stimulates its activity in a DNMT3L-independent manner. We determine the crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3 (active form) complexes at 3.82 and 2.90 Å resolution, respectively. Structural and biochemical analyses indicate that the ADD domain of DNMT3A interacts with and inhibits enzymatic activity of the catalytic domain (CD) through blocking its DNA-binding affinity. Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. The finding adds another layer of regulation of DNA methylation to ensure that the enzyme is mainly activated at proper targeting loci when unmethylated H3K4 is present, and strongly supports a negative correlation between H3K4me3 and DNA methylation across the mammalian genome. Our study provides a new insight into an unexpected autoinhibition and histone H3-induced activation of the de novo DNA methyltransferase after its initial genomic positioning. |
X Demographics
The data shown below were collected from the profiles of 12 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 25% |
| Japan | 2 | 17% |
| France | 1 | 8% |
| United Kingdom | 1 | 8% |
| Unknown | 5 | 42% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 10 | 83% |
| Science communicators (journalists, bloggers, editors) | 1 | 8% |
| Scientists | 1 | 8% |
Mendeley readers
The data shown below were compiled from readership statistics for 417 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | <1% |
| Japan | 2 | <1% |
| Bulgaria | 1 | <1% |
| India | 1 | <1% |
| Netherlands | 1 | <1% |
| Canada | 1 | <1% |
| Germany | 1 | <1% |
| United Kingdom | 1 | <1% |
| Spain | 1 | <1% |
| Other | 0 | 0% |
| Unknown | 405 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 110 | 26% |
| Researcher | 75 | 18% |
| Student > Master | 44 | 11% |
| Student > Bachelor | 40 | 10% |
| Student > Doctoral Student | 28 | 7% |
| Other | 55 | 13% |
| Unknown | 65 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 156 | 37% |
| Agricultural and Biological Sciences | 118 | 28% |
| Medicine and Dentistry | 22 | 5% |
| Chemistry | 14 | 3% |
| Neuroscience | 11 | 3% |
| Other | 26 | 6% |
| Unknown | 70 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 30. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 August 2017.
All research outputs
#1,115,422
of 22,769,322 outputs
Outputs from Nature
#32,516
of 90,829 outputs
Outputs of similar age
#13,881
of 260,467 outputs
Outputs of similar age from Nature
#590
of 1,026 outputs
Altmetric has tracked 22,769,322 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 90,829 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 99.3. This one has gotten more attention than average, scoring higher than 64% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 260,467 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 94% of its contemporaries.
We're also able to compare this research output to 1,026 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.