RRC ID 51801
Author Li JR, Suzuki T, Nishimura H, Kishima M, Maeda S, Suzuki H.
Title Asymmetric Regulation of Peripheral Genes by Two Transcriptional Regulatory Networks.
Journal PLoS One
Abstract 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.
Volume 11(8)
Pages e0160459
Published 2016-1-1
DOI 10.1371/journal.pone.0160459
PII PONE-D-16-17190
PMID 27483142
PMC PMC4970704
MeSH Cell Line Cellular Reprogramming* Fibroblasts / cytology Fibroblasts / metabolism* Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks* Genetic Vectors / chemistry Genetic Vectors / metabolism Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Humans LIM-Homeodomain Proteins / genetics LIM-Homeodomain Proteins / metabolism Lentivirus / genetics Lentivirus / metabolism Microarray Analysis Monocytes / cytology Monocytes / metabolism* Repressor Proteins / genetics Repressor Proteins / metabolism Skin / cytology Skin / metabolism Transcription Factors / genetics Transcription Factors / metabolism Transcription, Genetic* Transduction, Genetic Twist-Related Protein 1 / genetics Twist-Related Protein 1 / metabolism
IF 2.74
Times Cited 2
Human and Animal Cells NB1RGB(RCB0222)