التفاصيل البيبلوغرافية
| العنوان: |
A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development |
| المؤلفون: |
Tang WWC, Dietmann S, Irie N, Leitch HG, Floros VI, Bradshaw CR, Hackett JA, Chinnery PF, Surani MA |
| المصدر: |
Cell |
| بيانات النشر: |
Cell Press |
| المجموعة: |
Newcastle University Library ePrints Service |
| الوصف: |
Resetting of the epigenome in human primordial germ cells (hPGCs) is critical for development. We show that the transcriptional program of hPGCs is distinct from that in mice, with co-expression of somatic specifiers and naive pluripotency genes TFCP2L1 and KLF4. This unique gene regulatory network, established by SOX17 and BLIMP1, drives comprehensive germline DNA demethylation by repressing DNA methylation pathways and activating TET-mediated hydroxymethylation. Base-resolution methylome analysis reveals progressive DNA demethylation to basal levels in week 5-7 in vivo hPGCs. Concurrently, hPGCs undergo chromatin reorganization, X reactivation, and imprint erasure. Despite global hypomethylation, evolutionarily young and potentially hazardous retroelements, like SVA, remain methylated. Remarkably, some loci associated with metabolic and neurological disorders are also resistant to DNA demethylation, revealing potential for transgenerational epigenetic inheritance that may have phenotypic consequences. We provide comprehensive insight on early human germline transcriptional network and epigenetic reprogramming that subsequently impacts human development and disease. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| Relation: |
https://eprints.ncl.ac.uk/213848; https://eprints.ncl.ac.uk/fulltext.aspx?url=213848/25B6A5E6-BA5C-4869-814F-5EEC4BCD3B75.pdf&pub_id=213848 |
| الاتاحة: |
https://eprints.ncl.ac.uk/213848 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.120B74B5 |
| قاعدة البيانات: |
BASE |