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Comprehensive single cell-resolution analysis of the role of chromatin regulators in early C. elegans embryogenesis
- Source :
- Developmental Biology, 398(2), 153-162. Elsevier Inc.
- Publication Year :
- 2015
-
Abstract
- Chromatin regulators are widely expressed proteins with diverse roles in gene expression, nuclear organization, cell cycle regulation, pluripotency, physiology and development, and are frequently mutated in human diseases such as cancer. Their inhibition often results in pleiotropic effects that are difficult to study using conventional approaches. We have developed a semi-automated nuclear tracking algorithm to quantify the divisions, movements and positions of all nuclei during the early development of Caenorhabditis elegans and have used it to systematically study the effects of inhibiting chromatin regulators. The resulting high dimensional datasets revealed that inhibition of multiple regulators, including F55A3.3 (encoding FACT subunit SUPT16H), lin-53 (RBBP4/7), rba-1 (RBBP4/7), set-16 (MLL2/3), hda-1 (HDAC1/2), swsn-7 (ARID2), and let-526 (ARID1A/1B) affected cell cycle progression and caused chromosome segregation defects. In contrast, inhibition of cir-1 (CIR1) accelerated cell division timing in specific cells of the AB lineage. The inhibition of RNA polymerase II also accelerated these division timings, suggesting that normal gene expression is required to delay cell cycle progression in multiple lineages in the early embryo. Quantitative analyses of the dataset suggested the existence of at least two functionally distinct SWI/SNF chromatin remodeling complex activities in the early embryo, and identified a redundant requirement for the egl-27 and lin-40 MTA orthologs in the development of endoderm and mesoderm lineages. Moreover, our dataset also revealed a characteristic rearrangement of chromatin to the nuclear periphery upon the inhibition of multiple general regulators of gene expression. Our systematic, comprehensive and quantitative datasets illustrate the power of single cell-resolution quantitative tracking and high dimensional phenotyping to investigate gene function. Furthermore, the results provide an overview of the functions of essential chromatin regulators during the early development of an animal. publisher: Elsevier articletitle: Comprehensive single cell-resolution analysis of the role of chromatin regulators in early C. elegans embryogenesis journaltitle: Developmental Biology articlelink: http://dx.doi.org/10.1016/j.ydbio.2014.10.014 content_type: article copyright: Copyright © 2014 Elsevier Inc. All rights reserved. ispartof: Developmental Biology vol:398 issue:2 pages:153-162 ispartof: location:United States status: published
- Subjects :
- Embryo, Nonmammalian
Cell division
ARID1A
Embryonic Development
Chromatin regulators
Biology
Chromatin remodeling
Image analysis
Mesoderm
Single-cell analysis
SDG 3 - Good Health and Well-being
Chromosome Segregation
Animals
Humans
RBBP4
Cell Lineage
Epigenetics
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Molecular Biology
Genes, Helminth
Genetics
Cell Nucleus
Cell Cycle
Endoderm
Gene Expression Regulation, Developmental
Cell Biology
High dimensional phenotyping
Chromatin
Cell biology
Embryogenesis
C. elegans
RNA Interference
Gene expression
Single-Cell Analysis
Developmental Biology
Bivalent chromatin
Subjects
Details
- ISSN :
- 00121606
- Volume :
- 398
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....57975b237c477193c70e0b042b5cd0a1