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Deletion of HP1γ in cardiac myocytes affects H4K20me3 levels but does not impact cardiac growth

Overview of attention for article published in Epigenetics & Chromatin, April 2018
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Title
Deletion of HP1γ in cardiac myocytes affects H4K20me3 levels but does not impact cardiac growth
Published in
Epigenetics & Chromatin, April 2018
DOI 10.1186/s13072-018-0187-z
Pubmed ID
Authors

Kyohei Oyama, Danny El-Nachef, Chen Fang, Hidemi Kajimoto, Jeremy P. Brown, Prim B. Singh, W. Robb MacLellan

Abstract

Heterochromatin, which is formed when tri-methyl lysine 9 of histone H3 (H3K9me3) is bound by heterochromatin 1 proteins (HP1s), plays an important role in differentiation and senescence by silencing cell cycle genes. Cardiac myocytes (CMs) accumulate heterochromatin during differentiation and demethylation of H3K9me3 inhibits cell cycle gene silencing and cell cycle exit in CMs; however, it is unclear if this process is mediated by HP1s. In this study, we created a conditional CM-specific HP1 gamma (HP1γ) knockout (KO) mouse model and tested whether HP1γ is required for cell cycle gene silencing and cardiac growth. HP1γ KO mice were generated by crossing HP1γ floxed mice (fl) with mice expressing Cre recombinase driven by the Nkx2.5 (cardiac progenitor gene) promoter (Cre). We confirmed that deletion of critical exons of HP1γ led to undetectable levels of HP1γ protein in HP1γ KO (Cre;fl/fl) CMs. Analysis of cardiac size and function by echo revealed no significant differences between HP1γ KO and control (WT, Cre, fl/fl) mice. No significant difference in expression of cell cycle genes or cardiac-specific genes was observed. Global transcriptome analysis demonstrated a very moderate effect of HP1γ deletion on global gene expression, with only 51 genes differentially expressed in HP1γ KO CMs. We found that HP1β protein, but not HP1α, was significantly upregulated and that subnuclear localization of HP1β to perinuclear heterochromatin was increased in HP1γ KO CMs. Although HP1γ KO had no effect on H3K9me3 levels, we found a significant reduction in another major heterochromatin mark, tri-methylated lysine 20 of histone H4 (H4K20me3). These data indicate that HP1γ is dispensable for cell cycle exit and normal cardiac growth but has a significant role in maintaining H4K20me3 and regulating a limited number of genes in CMs.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 4 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 4 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 2 50%
Researcher 2 50%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 75%
Unknown 1 25%

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 16 October 2018.
All research outputs
#8,642,248
of 13,782,054 outputs
Outputs from Epigenetics & Chromatin
#330
of 414 outputs
Outputs of similar age
#163,312
of 272,239 outputs
Outputs of similar age from Epigenetics & Chromatin
#1
of 1 outputs
Altmetric has tracked 13,782,054 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 414 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.4. This one is in the 14th percentile – i.e., 14% 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 272,239 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them