TET2-and TDG-mediated changes are required for the acquisition of distinct histone modifications in divergent terminal differentiation of myeloid cells
NUCLEIC ACIDS RESEARCH
Authors: Garcia-Gomez, Antonio; Li, Tianlu; Kerick, Martin; Catala-Moll, Francesc; Comet, Natalia R.; Rodriguez-Ubreva, Javier; de la Rica, Lorenzo; Branco, Miguel R.; Martin, Javier; Ballestar, Esteban
Abstract
The plasticity of myeloid cells is illustrated by a diversity of functions including their role as effectors of innate immunity as macrophages (MACs) and bone remodelling as osteoclasts (OCs). TET2, a methylcytosine dioxygenase highly expressed in these cells and frequently mutated in myeloid leukemias, may be a key contributor to this plasticity. Through transcriptomic and epigenomic analyses, we investigated 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and gene expression changes in two divergent terminal myeloid differentiation processes, namely MAC and OC differentiation. MACs and OCs undergo highly similar 5hmC and 5mC changes, despite their wide differences in gene expression. Many TET2- and thymine-DNA glycosylase (TDG)-dependent 5mC and 5hmC changes directly activate the common terminalmyeloid differentiation programme. However, the acquisition of differential features between MACs and OCs also depends on TET2/TDG. In fact, 5mC oxidation precedes differential histone modification changes between MACs and OCs. TET2 and TDG downregulation impairs the acquisition of such differential histone modification and expression patterns at MAC-/OC-specific genes. We prove that the histone H3K4 methyltransferase SETD1A is differentially recruited between MACs and OCs in a TET2-dependent manner. We demonstrate a novel role of these enzymes in the establishment of specific elements of identity and function in terminal myeloid differentiation.
Hatching rate of Chinese sucker (Myxocyprinus asiaticus Bleeker) eggs exposed to total dissolved gas (TDG) supersaturation and the tolerance of juveniles to the interaction of TDG supersaturation and suspended sediment
AQUACULTURE RESEARCH
Authors: Li, Na; Fu, Chenghua; Zhang, Jing; Liu, Xiaoqing; Shi, Xiaotao; Yang, Yao; Shi, Haoran
Abstract
Flood discharge containing excessive suspended sediments (SS) can result in total dissolved gas (TDG) supersaturation downstream of dams. It has been confirmed that high TDG levels and excessive SS cause serious threats to fish survival. To explore the effects of TDG supersaturation on the hatchability of Chinese sucker (Myxocyprinus asiaticus Bleeker) eggs, eggs were exposed to 100%, 125%, 130% and 135% TDG supersaturated water. The results showed that the hatching rates were 78.25%, 75.35%, 71.30% and 67.50% at the 100%, 125%, 130% and 135% TDG respectively. The hatching rate decreased with increasing TDG levels. Furthermore, acute lethality experiments were carried out to investigate the interaction of TDG supersaturation and SS on Chinese sucker. Half-year-old juveniles were exposed to TDG supersaturated water with SS concentrations of 0, 200, 600 and 1,000 mg/L, and the TDG levels were 125%, 130%, 135% and 140% respectively. The fish exhibited abnormal behaviours and signs of gas bubble disease. Mortality increased with increasing TDG levels and SS concentrations. The Chinese suckers only survived for 2.5 hr at 140% TDG and 1,000 mg/L SS. Moreover, an increase in SS in TDG supersaturated water could cause a decrease in the median lethal time (LT50). When the TDG level reached 140%, the LT50 declines significantly at 600 and 1,000 mg/L SS. The interaction of TDG supersaturation and SS was significant at LT50 (F = 22.81, df = 9, p < 0.001). The results indicate that the combined effect of TDG and SS could be great on Chinese sucker.