Asymmetric Regulation of Peripheral Genes by Two Transcriptional Regulatory Networks

Transcriptional regulatory network (TRN) reconstitution and deconstruction occur simultaneously during reprogramming; however, it remains unclear how the starting and targeting TRNs regulate the induction and suppression of peripheral genes. Here we analyzed the regulation using direct cell reprogra...

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Bibliographic Details
Published in:PloS one 2016-08, Vol.11 (8), p.e0160459-e0160459
Main Authors: Li, Jing-Ru, Suzuki, Takahiro, Nishimura, Hajime, Kishima, Mami, Maeda, Shiori, Suzuki, Harukazu
Format: Article
Language:English
Subjects:
Analysis
Biology and Life Sciences
Cell Line
Cellular Reprogramming
Fibroblasts
Fibroblasts - cytology
Fibroblasts - metabolism
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Gene regulation
Gene Regulatory Networks
Genes
Genetic aspects
Genetic regulation
Genetic Vectors - chemistry
Genetic Vectors - metabolism
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Lentivirus - genetics
Lentivirus - metabolism
LIM-Homeodomain Proteins - genetics
LIM-Homeodomain Proteins - metabolism
Medicine and Health Sciences
Microarray Analysis
Monocytes
Monocytes - cytology
Monocytes - metabolism
Nuclear reprogramming
Physiological aspects
Regulation
Repressor Proteins - genetics
Repressor Proteins - metabolism
Research and Analysis Methods
Rodents
Skin
Skin - cytology
Skin - metabolism
Stem cells
Transcription
Transcription (Genetics)
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription, Genetic
Transduction, Genetic
Twist-Related Protein 1 - genetics
Twist-Related Protein 1 - metabolism
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Summary:Transcriptional regulatory network (TRN) reconstitution and deconstruction occur simultaneously during reprogramming; however, it remains unclear how the starting and targeting TRNs regulate the induction and suppression of peripheral genes. Here we analyzed the regulation using direct cell reprogramming from human dermal fibroblasts to monocytes as the platform. We simultaneously deconstructed fibroblastic TRN and reconstituted monocytic TRN; monocytic and fibroblastic gene expression were analyzed in comparison with that of fibroblastic TRN deconstruction only or monocytic TRN reconstitution only. Global gene expression analysis showed cross-regulation of TRNs. Detailed analysis revealed that knocking down fibroblastic TRN positively affected half of the upregulated monocytic genes, indicating that intrinsic fibroblastic TRN interfered with the expression of induced genes. In contrast, reconstitution of monocytic TRN showed neutral effects on the majority of fibroblastic gene downregulation. This study provides an explicit example that demonstrates how two networks together regulate gene expression during cell reprogramming processes and contributes to the elaborate exploration of TRNs.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0160459