The Emerging Roles of Fox Family Transcription Factors in Chromosome Replication, Organization, and Genome Stability
The forkhead box (Fox) transcription factors (TFs) are widespread from yeast to humans. Their mutations and dysregulation have been linked to a broad spectrum of malignant neoplasias. They are known as critical players in DNA repair, metabolism, cell cycle control, differentiation, and aging. Recent...
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MDPI AG
2020-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/1/258 |
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| author | Yue Jin Zhangqian Liang Huiqiang Lou |
| author_facet | Yue Jin Zhangqian Liang Huiqiang Lou |
| author_sort | Yue Jin |
| collection | DOAJ |
| description | The forkhead box (Fox) transcription factors (TFs) are widespread from yeast to humans. Their mutations and dysregulation have been linked to a broad spectrum of malignant neoplasias. They are known as critical players in DNA repair, metabolism, cell cycle control, differentiation, and aging. Recent studies, especially those from the simple model eukaryotes, revealed unexpected contributions of Fox TFs in chromosome replication and organization. More importantly, besides functioning as a canonical TF in cell signaling cascades and gene expression, Fox TFs can directly participate in DNA replication and determine the global replication timing program in a transcription-independent mechanism. Yeast Fox TFs preferentially recruit the limiting replication factors to a subset of early origins on chromosome arms. Attributed to their dimerization capability and distinct DNA binding modes, Fkh1 and Fkh2 also promote the origin clustering and assemblage of replication elements (replication factories). They can mediate long-range intrachromosomal and interchromosomal interactions and thus regulate the four-dimensional chromosome organization. The novel aspects of Fox TFs reviewed here expand their roles in maintaining genome integrity and coordinating the multiple essential chromosome events. These will inevitably be translated to our knowledge and new treatment strategies of Fox TF-associated human diseases including cancer. |
| first_indexed | 2024-03-12T09:08:33Z |
| format | Article |
| id | doaj.art-012e676eadf0451b851ced30e87d80a3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T09:08:33Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-012e676eadf0451b851ced30e87d80a32023-09-02T15:06:08ZengMDPI AGCells2073-44092020-01-019125810.3390/cells9010258cells9010258The Emerging Roles of Fox Family Transcription Factors in Chromosome Replication, Organization, and Genome StabilityYue Jin0Zhangqian Liang1Huiqiang Lou2Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, No.2 Yuan-Ming-Yuan West Road, Beijing 100193, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, No.2 Yuan-Ming-Yuan West Road, Beijing 100193, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, No.2 Yuan-Ming-Yuan West Road, Beijing 100193, ChinaThe forkhead box (Fox) transcription factors (TFs) are widespread from yeast to humans. Their mutations and dysregulation have been linked to a broad spectrum of malignant neoplasias. They are known as critical players in DNA repair, metabolism, cell cycle control, differentiation, and aging. Recent studies, especially those from the simple model eukaryotes, revealed unexpected contributions of Fox TFs in chromosome replication and organization. More importantly, besides functioning as a canonical TF in cell signaling cascades and gene expression, Fox TFs can directly participate in DNA replication and determine the global replication timing program in a transcription-independent mechanism. Yeast Fox TFs preferentially recruit the limiting replication factors to a subset of early origins on chromosome arms. Attributed to their dimerization capability and distinct DNA binding modes, Fkh1 and Fkh2 also promote the origin clustering and assemblage of replication elements (replication factories). They can mediate long-range intrachromosomal and interchromosomal interactions and thus regulate the four-dimensional chromosome organization. The novel aspects of Fox TFs reviewed here expand their roles in maintaining genome integrity and coordinating the multiple essential chromosome events. These will inevitably be translated to our knowledge and new treatment strategies of Fox TF-associated human diseases including cancer.https://www.mdpi.com/2073-4409/9/1/258dna replicationchromatin interactiontranscription-independentchromosome domainreplication-transcription conflictscell fate decision |
| spellingShingle | Yue Jin Zhangqian Liang Huiqiang Lou The Emerging Roles of Fox Family Transcription Factors in Chromosome Replication, Organization, and Genome Stability Cells dna replication chromatin interaction transcription-independent chromosome domain replication-transcription conflicts cell fate decision |
| title | The Emerging Roles of Fox Family Transcription Factors in Chromosome Replication, Organization, and Genome Stability |
| title_full | The Emerging Roles of Fox Family Transcription Factors in Chromosome Replication, Organization, and Genome Stability |
| title_fullStr | The Emerging Roles of Fox Family Transcription Factors in Chromosome Replication, Organization, and Genome Stability |
| title_full_unstemmed | The Emerging Roles of Fox Family Transcription Factors in Chromosome Replication, Organization, and Genome Stability |
| title_short | The Emerging Roles of Fox Family Transcription Factors in Chromosome Replication, Organization, and Genome Stability |
| title_sort | emerging roles of fox family transcription factors in chromosome replication organization and genome stability |
| topic | dna replication chromatin interaction transcription-independent chromosome domain replication-transcription conflicts cell fate decision |
| url | https://www.mdpi.com/2073-4409/9/1/258 |
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