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Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic transcriptional network coordinate chondrocyte differentiation transitions

Tan, Zhijia ; Niu, Ben ; Tsang, Kwok Yeung ; Melhado, Ian G ; Ohba, Shinsuke ; He, Xinjun ; Huang, Yongheng ; Wang, Cheng ; McMahon, Andrew P ; Jauch, Ralf ; Chan, Danny ; Zhang, Michael Q ; Cheah, Kathryn S E Barsh, Gregory S.

PLoS genetics, 2018-04, Vol.14 (4), p.e1007346 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic transcriptional network coordinate chondrocyte differentiation transitions
Autor: Tan, Zhijia ; Niu, Ben ; Tsang, Kwok Yeung ; Melhado, Ian G ; Ohba, Shinsuke ; He, Xinjun ; Huang, Yongheng ; Wang, Cheng ; McMahon, Andrew P ; Jauch, Ralf ; Chan, Danny ; Zhang, Michael Q ; Cheah, Kathryn S E
Barsh, Gregory S.
Assuntos: Animals ; Binding sites ; Biochemistry ; Biology ; Biology and Life Sciences ; Bone Development - genetics ; Bone Development - physiology ; Bone growth ; Cartilage cells ; Cell Differentiation - genetics ; Cell Differentiation - physiology ; Chondrocytes ; Chondrocytes - cytology ; Chondrocytes - metabolism ; Chondrogenesis ; Chondrogenesis - genetics ; Chondrogenesis - physiology ; Competition ; Cooperation ; Cooperativity ; Core Binding Factor alpha Subunits - genetics ; Core Binding Factor alpha Subunits - metabolism ; Deoxyribonucleic acid ; DNA ; Female ; Gene expression ; Gene Regulatory Networks ; Genetic aspects ; Genetic regulation ; Genetic research ; Genomes ; Growth plate ; Growth Plate - cytology ; Growth Plate - growth & development ; Growth Plate - metabolism ; Hepatocyte Nuclear Factor 3-beta - genetics ; Hepatocyte Nuclear Factor 3-beta - metabolism ; Hypertrophy ; Laboratories ; Medical research ; Medicine ; Medicine and Health Sciences ; MEF2 Transcription Factors - genetics ; MEF2 Transcription Factors - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Models, Biological ; Myocyte enhancer factor 2 ; Ontology ; Physical sciences ; Physiological aspects ; Research and Analysis Methods ; Signal Transduction ; Software ; Sox9 protein ; SOX9 Transcription Factor - genetics ; SOX9 Transcription Factor - metabolism ; Stem cells ; Supervision ; Transcription factors ; Transcriptional Activation ; Zinc Finger Protein GLI1 - genetics ; Zinc Finger Protein GLI1 - metabolism
É parte de: PLoS genetics, 2018-04, Vol.14 (4), p.e1007346
Notas: new_version
Current address: Department of Bioengineering, the University of Tokyo, Tokyo, Japan
Current address: Group Structure Biochemistry, Institute for Chemistry and Biochemistry, Free University Berlin, Berlin, Germany
The authors have declared that no competing interests exist.
Descrição: The growth plate mediates bone growth where SOX9 and GLI factors control chondrocyte proliferation, differentiation and entry into hypertrophy. FOXA factors regulate hypertrophic chondrocyte maturation. How these factors integrate into a Gene Regulatory Network (GRN) controlling these differentiation transitions is incompletely understood. We adopted a genome-wide whole tissue approach to establish a Growth Plate Differential Gene Expression Library (GP-DGEL) for fractionated proliferating, pre-hypertrophic, early and late hypertrophic chondrocytes, as an overarching resource for discovery of pathways and disease candidates. De novo motif discovery revealed the enrichment of SOX9 and GLI binding sites in the genes preferentially expressed in proliferating and prehypertrophic chondrocytes, suggesting the potential cooperation between SOX9 and GLI proteins. We integrated the analyses of the transcriptome, SOX9, GLI1 and GLI3 ChIP-seq datasets, with functional validation by transactivation assays and mouse mutants. We identified new SOX9 targets and showed SOX9-GLI directly and cooperatively regulate many genes such as Trps1, Sox9, Sox5, Sox6, Col2a1, Ptch1, Gli1 and Gli2. Further, FOXA2 competes with SOX9 for the transactivation of target genes. The data support a model of SOX9-GLI-FOXA phasic GRN in chondrocyte development. Together, SOX9-GLI auto-regulate and cooperate to activate and repress genes in proliferating chondrocytes. Upon hypertrophy, FOXA competes with SOX9, and control toward terminal differentiation passes to FOXA, RUNX, AP1 and MEF2 factors.
Editor: United States: Public Library of Science
Idioma: Inglês

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Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic transcriptional network coordinate chondrocyte differentiation transitions

Tan, Zhijia ; Niu, Ben ; Tsang, Kwok Yeung ; Melhado, Ian G ; Ohba, Shinsuke ; He, Xinjun ; Huang, Yongheng ; Wang, Cheng ; McMahon, Andrew P ; Jauch, Ralf ; Chan, Danny ; Zhang, Michael Q ; Cheah, Kathryn S E Barsh, Gregory S.

United States: Public Library of Science

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