HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development

Rutkowski, Timothy P.; Kohn, Anat; Sharma, Deepika; Ren, Yinshi; Mirando, Anthony J.; Hilton, Matthew J.

doi:10.1242/dev.140608

Cited by 2 publications

(2 citation statements)

References 20 publications

(42 reference statements)

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“…Prominent members are the Hairy/Enhancer of Split-related HES and HEY transcriptional repressors, whose genes are direct targets of NOTCH signaling. HES1 and HES5 delay the differentiation of SSCs into chondrocytes and facilitate GPC hypertrophy ([142]. As for HIF1α, a key target might be Sox9 .…”

Section: Basic-domain Transcription Factorsmentioning

confidence: 99%

Transcriptional control of chondrocyte specification and differentiation

Liu

Samsa

Zhou

et al. 2017

Seminars in Cell & Developmental Biology

142

112

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A milestone in the evolutionary emergence of vertebrates was the invention of cartilage, a tissue that has key roles in modeling, protecting and complementing the bony skeleton. Cartilage is elaborated and maintained by chondrocytes. These cells derive from multipotent skeletal progenitors and they perform highly specialized functions as they proceed through sequential lineage commitment and differentiation steps. They form cartilage primordia, the primary skeleton of the embryo. They then transform these primordia either into cartilage growth plates, temporary drivers of skeletal elongation and endochondral ossification, or into permanent tissues, namely articular cartilage. Chondrocyte fate decisions and differentiated activities are controlled by numerous extrinsic and intrinsic cues, and they are implemented at the gene expression level by transcription factors. The latter are the focus of this review. Meritorious efforts from many research groups have led over the last two decades to the identification of dozens of key chondrogenic transcription factors. These regulators belong to all types of transcription factor families. Some have master roles at one or several differentiation steps. They include SOX9 and RUNX2/3. Others decisively assist or antagonize the activities of these masters. They include TWIST1, SOX5/6, and MEF2C/D. Many more have tissue-patterning roles and regulate cell survival, proliferation and the pace of cell differentiation. They include, but are not limited to, homeodomain-containing proteins and growth factor signaling mediators. We here review current knowledge of all these factors, one superclass, class, and family at a time. We then compile all knowledge into transcriptional networks. We also identify remaining gaps in knowledge and directions for future research to fill these gaps and thereby provide novel insights into cartilage disease mechanisms and treatment options.

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Section: Basic-domain Transcription Factorsmentioning

confidence: 99%

Transcriptional control of chondrocyte specification and differentiation

Liu

Samsa

Zhou

et al. 2017

Seminars in Cell & Developmental Biology

142

112

View full text Add to dashboard Cite

show abstract

“…There was a match to ELF3, a transcription factor important during chondrogenesis and in cartilage degradation in OA . Other matches include the HES and HEY family of transcription factors that are involved in chondrocyte hypertrophy during development (Table S6). The strong promoter state (2_TssS) also contained motifs belonging to transcription factors important in chondrogenesis such as SOX9 and ELF3 but also matched motifs of general transcription factors such as SP1 and the ETS family of transcription factors (Table S7).…”

Section: Resultsmentioning

confidence: 99%

Histone ChIP‐Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell‐type specificity

et al. 2020

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Epigenetic mechanisms are known to regulate gene expression during chondrogenesis. In this study, we have characterized the epigenome during the in vitro differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes. Chromatin immunoprecipitation followed by next‐generation sequencing (ChIP‐seq) was used to assess a range of N‐terminal posttranscriptional modifications (marks) to histone H3 lysines (H3K4me3, H3K4me1, H3K27ac, H3K27me3, and H3K36me3) in both hMSCs and differentiated chondrocytes. Chromatin states were characterized using histone ChIP‐seq and cis‐regulatory elements were identified in chondrocytes. Chondrocyte enhancers were associated with chondrogenesis‐related gene ontology (GO) terms. In silico analysis and integration of DNA methylation data with chondrogenesis chromatin states revealed that enhancers marked by histone marks H3K4me1 and H3K27ac were de‐methylated during in vitro chondrogenesis. Similarity analysis between hMSC and chondrocyte chromatin states defined in this study with epigenomes of cell‐types defined by the Roadmap Epigenomics project revealed that enhancers are more distinct between cell‐types compared to other chromatin states. Motif analysis revealed that the transcription factor SOX9 is enriched in chondrocyte enhancers. Luciferase reporter assays confirmed that chondrocyte enhancers characterized in this study exhibited enhancer activity which may be modulated by DNA methylation and SOX9 overexpression. Altogether, these integrated data illustrate the cross‐talk between different epigenetic mechanisms during chondrocyte differentiation.

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HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development

Cited by 2 publications

References 20 publications

Transcriptional control of chondrocyte specification and differentiation

Transcriptional control of chondrocyte specification and differentiation

Histone ChIP‐Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell‐type specificity

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