Maternal KLF17 controls zygotic genome activation by acting as a messenger for RNA Pol II recruitment in mouse embryos
Copyright © 2024 Elsevier Inc. All rights reserved..
Initiation of timely and sufficient zygotic genome activation (ZGA) is crucial for the beginning of life, yet our knowledge of transcription factors (TFs) contributing to ZGA remains limited. Here, we screened the proteome of early mouse embryos after cycloheximide (CHX) treatment and identified maternally derived KLF17 as a potential TF for ZGA genes. Using a conditional knockout (cKO) mouse model, we further investigated the role of maternal KLF17 and found that it promotes embryonic development and full fertility. Mechanistically, KLF17 preferentially binds to promoters and recruits RNA polymerase II (RNA Pol II) in early 2-cell embryos, facilitating the expression of major ZGA genes. Maternal Klf17 knockout resulted in a downregulation of 9% of ZGA genes and aberrant RNA Pol II pre-configuration, which could be partially rescued by introducing exogenous KLF17. Overall, our study provides a strategy for screening essential ZGA factors and identifies KLF17 as a crucial TF in this process.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
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| Enthalten in: |
Developmental cell - 59(2024), 5 vom: 11. März, Seite 613-626.e6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, Yue [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 15.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.devcel.2024.01.013 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368146154 |
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| 520 | |a Initiation of timely and sufficient zygotic genome activation (ZGA) is crucial for the beginning of life, yet our knowledge of transcription factors (TFs) contributing to ZGA remains limited. Here, we screened the proteome of early mouse embryos after cycloheximide (CHX) treatment and identified maternally derived KLF17 as a potential TF for ZGA genes. Using a conditional knockout (cKO) mouse model, we further investigated the role of maternal KLF17 and found that it promotes embryonic development and full fertility. Mechanistically, KLF17 preferentially binds to promoters and recruits RNA polymerase II (RNA Pol II) in early 2-cell embryos, facilitating the expression of major ZGA genes. Maternal Klf17 knockout resulted in a downregulation of 9% of ZGA genes and aberrant RNA Pol II pre-configuration, which could be partially rescued by introducing exogenous KLF17. Overall, our study provides a strategy for screening essential ZGA factors and identifies KLF17 as a crucial TF in this process | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a KLF17 | |
| 650 | 4 | |a RNA Pol II pre-configuration | |
| 650 | 4 | |a early embryonic development | |
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| 650 | 4 | |a zygotic genome activation | |
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| 700 | 1 | |a Wang, Yuxiang |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yuanlin |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Maosheng |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Siqi |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yueshuai |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Qiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a He, Anlan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Jiongsong |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Xuejiang |e verfasserin |4 aut | |
| 700 | 1 | |a Shu, Wenjie |e verfasserin |4 aut | |
| 700 | 1 | |a Huo, Ran |e verfasserin |4 aut | |
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