Tính linh hoạt của methyl hóa DNA trong quá trình kích hoạt và phân biệt tế bào T ở chuột

Springer Science and Business Media LLC - Tập 13 - Trang 1-19 - 2012
Yan Li1,2, Guobing Chen2, Lina Ma2, Stephen J Ohms3, Chao Sun1, M Frances Shannon2,4, Jun Y Fan2
1College of Animal Science & Technology, Northwest A&F University, P. R. China
2Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
3ACRF Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
4The University of Canberra, Canberra, Australia

Tóm tắt

Các tế bào T trợ giúp CD4+ lưu hành được kích hoạt thông qua các tương tác với các tế bào trình diện kháng nguyên và trải qua quá trình phân biệt thành các nhóm tế bào T trợ giúp cụ thể tùy thuộc vào loại kháng nguyên gặp phải. Hơn nữa, thành phần tương đối của quần thể tế bào T CD4+ lưu hành thay đổi khi động vật trưởng thành, với tỷ lệ phần trăm ngày càng tăng của quần thể là các tế bào ghi nhớ/tế bào có hiệu ứng. Ở đây, chúng tôi báo cáo về bản chất rất linh hoạt của methyl hóa DNA ở mức toàn bộ bộ gen khi các tế bào T trải qua sự kích hoạt, phân biệt và lão hóa. Đáng lưu ý là các phát hiện cho thấy methyl hóa DNA diễn ra nhanh chóng sau khi tế bào T được kích hoạt và rằng tất cả các quần thể tế bào T đã phân biệt đều có mức độ methyl hóa toàn cầu thấp hơn so với quần thể chưa phân biệt. Ngoài ra, các tế bào T từ chuột già cho thấy mức độ methyl hóa DNA giảm, điều này có thể được giải thích chủ yếu do sự gia tăng trong phần tế bào ghi nhớ/tế bào có hiệu ứng. Mặc dù có sự thay đổi đáng kể ở mức độ toàn bộ bộ gen, nhưng các thay đổi trong methyl hóa DNA ở từng gen lại bị giới hạn ở các loại tế bào cụ thể. Sự thay đổi trong biểu hiện của các enzyme liên quan đến methyl hóa và demethyl hóa DNA phản ánh trong hầu hết các trường hợp sự thay đổi quan sát được trong trạng thái methyl hóa DNA toàn bộ bộ gen. Chúng tôi đã chứng minh rằng methyl hóa DNA là động và linh hoạt ở các tế bào T CD4+ và thay đổi nhanh chóng cả theo cách toàn bộ bộ gen và có mục tiêu trong quá trình kích hoạt và phân biệt tế bào T. Những thay đổi này đi kèm với các thay đổi song song trong các phức hợp enzym đã được liên quan đến methyl hóa và demethyl hóa DNA, điều này ngụ ý rằng sự cân bằng giữa các hoạt động đối kháng này có thể đóng vai trò trong việc duy trì hồ sơ methyl hóa của một loại tế bào nhất định nhưng cũng cho phép linh hoạt trong quần thể tế bào cần phải phản ứng nhanh chóng với các tín hiệu môi trường.

Từ khóa

#DNA methylation #T cells #activation #differentiation #memory cells #effector cells

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