title: Asymmetric Regulation of Peripheral Genes by Two Transcriptional Regulatory Networks.
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.
authors.affiliation: Division of Genomic Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan.
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Li
authors.affiliation: Division of Genomic Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Division of Genomic Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: Division of Genomic Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Kishima
authors.affiliation: Division of Genomic Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Division of Genomic Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan.
authors.forename: Harukazu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D002460:Cell Line; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C492149:LHX9 protein, human; D060850:LIM-Homeodomain Proteins; C498490:OSR1 protein, human; C082157:PRRX1 protein, human; D012097:Repressor Proteins; C486274:TWIST2 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1