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DNA methyltransferase 1 functions through C/ebpa to maintain hematopoietic stem and progenitor cells in zebrafish

Overview of attention for article published in Journal of Hematology & Oncology, February 2015
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Title
DNA methyltransferase 1 functions through C/ebpa to maintain hematopoietic stem and progenitor cells in zebrafish
Published in
Journal of Hematology & Oncology, February 2015
DOI 10.1186/s13045-015-0115-7
Pubmed ID
Authors

Xiaohui Liu, Xiaoe Jia, Hao Yuan, Ke Ma, Yi Chen, Yi Jin, Min Deng, Weijun Pan, Saijuan Chen, Zhu Chen, Hugues de The, Leonard I Zon, Yi Zhou, Jun Zhou, Jun Zhu

Abstract

DNA methyltransferase 1 (Dnmt1) regulates expression of many critical genes through maintaining parental DNA methylation patterns on daughter DNA strands during mitosis. It is essential for embryonic development and diverse biological processes, including maintenance of hematopoietic stem and progenitor cells (HSPCs). However, the precise molecular mechanism of how Dnmt1 is involved in HSPC maintenance remains unexplored. An N-ethyl-N-nitrosourea (ENU)-based genetic screening was performed to identify putative mutants with defects in definitive HSPCs during hematopoiesis in zebrafish. The expression of hematopoietic markers was analyzed via whole mount in situ hybridization assay (WISH). Positional cloning approach was carried out to identify the gene responsible for the defective definitive hematopoiesis in the mutants. Analyses of the mechanism were conducted by morpholino-mediated gene knockdown, mRNA injection rescue assays, anti-phosphorylated histone H3 (pH3) immunostaining and TUNEL assay, quantitative real-time PCR, and bisulfite sequencing analysis. A heritable mutant line with impaired HSPCs of definitive hematopoiesis was identified. Positional cloning demonstrated that a stop codon mutation was introduced in dnmt1 which resulted in a predicted truncated Dnmt1 lacking the DNA methylation catalytic domain. Molecular analysis revealed that expression of CCAAT/enhancer-binding protein alpha (C/ebpa) was upregulated, which correlated with hypomethylation of CpG islands in the regulation regions of cebpa gene in Dnmt1 deficient HSPCs. Overexpression of a transcriptional repressive SUMO-C/ebpa fusion protein could rescue hematological defects in the dnmt1 mutants. Finally, dnmt1 and cebpa double null embryos exhibited no obvious abnormal hematopoiesis indicated that the HSPC defects triggered by dnmt1 mutation were C/ebpa dependent. Dnmt1 is required for HSPC maintenance via cebpa regulation during definitive hematopoiesis in zebrafish.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 21%
Student > Bachelor 7 17%
Researcher 5 12%
Student > Master 4 10%
Student > Postgraduate 3 7%
Other 5 12%
Unknown 9 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 14 33%
Biochemistry, Genetics and Molecular Biology 12 29%
Medicine and Dentistry 3 7%
Chemical Engineering 1 2%
Social Sciences 1 2%
Other 3 7%
Unknown 8 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 February 2015.
All research outputs
#15,325,004
of 22,792,160 outputs
Outputs from Journal of Hematology & Oncology
#777
of 1,191 outputs
Outputs of similar age
#151,024
of 255,204 outputs
Outputs of similar age from Journal of Hematology & Oncology
#15
of 19 outputs
Altmetric has tracked 22,792,160 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,191 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.7. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
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 255,204 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 19 others from the same source and published within six weeks on either side of this one. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.