The nuclear bodies formed by histone demethylase KDM7A
- PDF / 2,737,665 Bytes
- 8 Pages / 595.276 x 785.197 pts Page_size
- 29 Downloads / 155 Views
Protein & Cell
LETTER
Dear Editor, In the nucleus of higher eukaryotes, chromatin occupies only a small proportion of the nuclear space, while many proteins and RNAs segregate into membrane-less nuclear bodies (NBs). These NBs follow a stochastic or ordered assembly model and constantly exchange components with the surrounding nucleoplasm (Jain et al., 2016). Typical NBs include nucleoli, nuclear speckles, paraspeckles, PML bodies, Cajal bodies, polycomb bodies and Sam68 bodies, which play critical roles in various biological processes such as ribosome assembly, RNA processing, and protein modification. The dysfunction of nuclear bodies may cause diseases, such as cancer (Li et al., 2019). It has been revealed that NBs involve in the stress response. Stress could lead to cell-cycle arrest, apoptosis or reorganization of the nuclear architecture. NBs respond quickly to stress, altering their components or structure to help the cell to recover from abnormal states. Nucleolus, as the largest nuclear body, is regarded as a central hub in coordinating cellular stress response by regulating ribosome subunit biogenesis and cell cycle progression. In response to stress, nucleolus can control the activity of the tumor suppressor protein p53 or crosstalk with Cajal bodies (Boulon et al., 2010). As a ROS sensor, PML can activate oxidative stress-responsive p53 targets during the PML body biogenesis, which is dependent on the PML RING tetramerization (Wang et al., 2018). The lysine demethylase 7A (KDM7A) functions as a dualspecificity demethylase for histone H3 Lys 9 and Lys 27 dimethylation (H3K9me2 and H3K27me2), two repressive histone marks. Under long-term nutrient starvation, the expression level of KDM7A increased in cancer cells (Osawa et al., 2011) (Fig. 1A). We were asking whether the increase of KDM7A links to NBs under environmental stimuli. Indeed, the immunofluorescence signal of KDM7A gathered as the larger size foci after 48-hour serum deprivation in HeLa cells (Fig. 1B and 1C). Most of these KDM7A foci are different from known NBs such as nuclear speckles, paraspeckles, PML bodies, Cajal bodies, polycomb bodies, Sam68 bodies, and RNA polymerase II condensates (Figs. 1D, S1A and S1B). We thus named these nuclear KDM7A foci as K-bodies. Additionally, we tested other
© The Author(s) 2020
stresses: the high salt treatment, but not amino acids starvation, can also lead to enlarged KDM7A foci (Fig. S1C–F), which implied that KDM7A condensates may form when cells undergo intense stresses. Furthermore, the expression of exogenous N-terminal tagged GFP-KDM7A (nGFP-KDM7A), which retains its histone demethylase activity (Fig. S2A), can also induce KDM7A foci (Fig. S2B). These nGFP-KDM7A foci can be clearly detected by immunofluorescence with the antiKDM7A antibody, thereby validating the specificity of this antibody (Fig. S2C). Immunofluorescence imaging revealed that the nGFP-KDM7A foci are also largely independent of tested NBs (Figs. 1E, 1F and S2D). To investigate the function of K-bodies, we analyzed KDM7A-associated p
Data Loading...
