Tip60/KAT5 Histone Acetyltransferase Is Required for Maintenance and Neurogenesis of Embryonic Neural Stem Cells.

Autor: Tominaga K; Division of Structural Biochemistry, Department of Biochemistry, Jichi Medical University, Tochigi 321-0498, Japan.; Division of Functional Biochemistry, Department of Biochemistry, Jichi Medical University, Tochigi 321-0498, Japan., Sakashita E; Division of Functional Biochemistry, Department of Biochemistry, Jichi Medical University, Tochigi 321-0498, Japan., Kasashima K; Division of Functional Biochemistry, Department of Biochemistry, Jichi Medical University, Tochigi 321-0498, Japan., Kuroiwa K; Division of Functional Biochemistry, Department of Biochemistry, Jichi Medical University, Tochigi 321-0498, Japan., Nagao Y; Center for Experimental Medicine, Jichi Medical University, Tochigi 321-0498, Japan., Iwamori N; Department of Agriculture, Kyushu University, Fukuoka 819-0395, Japan., Endo H; Division of Functional Biochemistry, Department of Biochemistry, Jichi Medical University, Tochigi 321-0498, Japan.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Jan 20; Vol. 24 (3). Date of Electronic Publication: 2023 Jan 20.
DOI: 10.3390/ijms24032113
Abstrakt: Epigenetic regulation via epigenetic factors in collaboration with tissue-specific transcription factors is curtail for establishing functional organ systems during development. Brain development is tightly regulated by epigenetic factors, which are coordinately activated or inactivated during processes, and their dysregulation is linked to brain abnormalities and intellectual disability. However, the precise mechanism of epigenetic regulation in brain development and neurogenesis remains largely unknown. Here, we show that Tip60/KAT5 deletion in neural stem/progenitor cells (NSCs) in mice results in multiple abnormalities of brain development. Tip60-deficient embryonic brain led to microcephaly, and proliferating cells in the developing brain were reduced by Tip60 deficiency. In addition, neural differentiation and neuronal migration were severely affected in Tip60-deficient brains. Following neurogenesis in developing brains, gliogenesis started from the earlier stage of development in Tip60-deficient brains, indicating that Tip60 is involved in switching from neurogenesis to gliogenesis during brain development. It was also confirmed in vitro that poor neurosphere formation, proliferation defects, neural differentiation defects, and accelerated astrocytic differentiation in mutant NSCs are derived from Tip60-deficient embryonic brains. This study uncovers the critical role of Tip60 in brain development and NSC maintenance and function in vivo and in vitro.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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