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Published on: September 7, 2017
Developmental control of the DNA replication and transcription programs.
Jared Nordman1, Sharon Li, Thomas Eng
1Department of Biology, Whitehead Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Differential replication, where DNA copy number varies within polyploid cells, is common in Drosophila. This study reveals tissue-specific patterns of underreplication, controlled by SUUR, and shows transcriptional silencing and underreplication can be uncoupled.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Polyploid cells with >2C DNA content are common in differentiated tissues.
- Differential replication, altering DNA copy number in specific genomic regions, is a known phenomenon.
- The developmental role and prevalence of differential replication remain largely unexplored.
Purpose of the Study:
- To investigate the frequency and patterns of differential DNA replication in Drosophila larval tissues.
- To identify common and tissue-specific sites of underreplication.
- To explore the relationship between underreplication and transcriptional activity.
Main Methods:
- Genome-wide array-based comparative genomic hybridization (aCGH) was used to profile DNA copy number variations.
- Larval fat body, midgut, and salivary gland tissues from Drosophila were analyzed.
- mRNA sequencing (mRNA-seq) was employed to assess transcriptional activity in underreplicated regions.
Main Results:
- Common and tissue-specific sites of euchromatic underreplication were identified across larval fat body, midgut, and salivary gland.
- Both common and tissue-specific underreplication were found to be dependent on the Suppressor of Underreplication (SUUR) protein.
- Transcriptional silencing was generally observed in underreplicated regions of the midgut and salivary gland, but uncoupled from underreplication in the fat body.
Conclusions:
- Differential replication is a prevalent strategy in Drosophila development, with both conserved and tissue-specific mechanisms.
- The SUUR protein plays a critical role in regulating both common and tissue-specific underreplication.
- Transcriptional silencing and DNA underreplication can be mechanistically separated, particularly in the larval fat body.
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