Các retrotransposon Alu điều chỉnh sự biểu hiện của Nanog thông qua những thay đổi động trong cấu trúc chromatin vùng thông qua thụ thể hydrocarbon dị vòng
Tóm tắt
Việc ức chế phiên mã của Nanog là một dấu hiệu quan trọng trong quá trình biệt hóa tế bào gốc. Các biến đổi chromatin đã được liên kết với hồ sơ epigen của gen Nanog, nhưng việc tổ chức chromatin có thực sự đóng vai trò nguyên nhân trong việc điều tiết Nanog vẫn chưa rõ ràng. Tại đây, chúng tôi báo cáo rằng sự hình thành vòng chromatin ở locus Nanog diễn ra đồng thời với sự giảm điều chỉnh phiên mã của nó trong quá trình biệt hóa tế bào NTERA-2 ở người. Chúng tôi phát hiện rằng hai yếu tố Alu bao quanh gen Nanog đã liên kết với thụ thể hydrocarbon dị vòng (AhR) và protein cách ly CTCF trong quá trình biệt hóa tế bào. Việc kết nối này đã thay đổi hồ sơ các biến đổi histone ức chế gần Nanog, có thể dẫn đến sự cách ly gen thông qua việc hình thành vòng chromatin giữa hai yếu tố Alu. Sử dụng sàng lọc proteomic được hướng dẫn bởi dCAS9, chúng tôi phát hiện rằng sự tương tác của methyltransferase histone PRMT1 và yếu tố lắp ghép chromatin CHAF1B với hai yếu tố Alu bao quanh Nanog là cần thiết cho việc hình thành vòng chromatin và ức chế Nanog. Do đó, kết quả của chúng tôi phát hiện ra một cơ chế điều khiển sự biểu hiện của Nanog trong quá trình biệt hóa tế bào, được điều chỉnh bởi retrotransposon và thúc đẩy bởi chromatin.
Từ khóa
#Nanog #tế bào gốc #chromatin #retrotransposon #sự biểu hiện genTài liệu tham khảo
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