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PloS one
2019;14 (1): e0211333.

Unique and overlapping GLI1 and GLI2 transcriptional targets in neoplastic chondrocytes.

Shabana Amanda Ali, Ben Niu, Kathryn S E Cheah, Benjamin Alman
Author Information
  1. Shabana Amanda Ali: Genetics and Development, Krembil Research Institute, Toronto, Ontario, Canada. ORCID
  2. Ben Niu: School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
  3. Kathryn S E Cheah: School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
  4. Benjamin Alman: Department of Orthopaedic Surgery, Duke University, Durham, North Carolina, United States of America.
PMID: 30695055 DOI: 10.1371/journal.pone.0211333

Abstract

Excessive Hedgehog (Hh) signaling in chondrocytes is sufficient to cause formation of enchondroma-like lesions which can progress to chondrosarcoma. To elucidate potential underlying mechanisms, we identified GLI1 and GLI2 target genes in human chondrosarcoma. Using chromatin immunoprecipitation (ChIP) sequencing and microarray data, in silico analyses were conducted to identify and characterize unique and overlapping GLI1 and GLI2 binding regions in neoplastic chondrocytes. After overlaying microarray data from human chondrosarcoma, 204 upregulated and 106 downregulated genes were identified as Hh-responsive Gli binding targets. After overlaying published Gli ChIP-on-chip data from mouse, 48 genes were identified as potential direct downstream targets of Hedgehog signaling with shared GLI binding regions in evolutionarily conserved DNA elements. Among these was BMP2, pointing to potential cross-talk between TGF beta signaling and Hh signaling. Our identification of potential target genes that are unique and common to GLI1 and GLI2 in neoplastic chondrocytes contributes to elucidating potential pathways through which Hh signaling impacts cartilage tumor biology.

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Grants

  1. R01 AR066765/NIAMS NIH HHS

MeSH Term

Animals
Bone Neoplasms
Chondrosarcoma
Chromatin Immunoprecipitation
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Hedgehog Proteins
Humans
Mice
Nuclear Proteins
Oligonucleotide Array Sequence Analysis
Protein Binding
Signal Transduction
Tumor Cells, Cultured
Zinc Finger Protein GLI1
Zinc Finger Protein Gli2

Chemicals

GLI1 protein, human
GLI2 protein, human
Hedgehog Proteins
Nuclear Proteins
Zinc Finger Protein GLI1
Zinc Finger Protein Gli2
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 3

Word Cloud

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