Transcriptional control of transglutaminase 2 expression in mouse apoptotic thymocytes

Katalin Sándor, Bence Daniel, Bea Kiss, Fruzsina Kovács, Z. Szondy

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Transglutaminase 2 (TGM2) is a ubiquitously expressed multifunctional protein, which participates in various biological processes including thymocyte apoptosis. As a result, the transcriptional regulation of the gene is complex and must depend on the cell type. Previous studies from our laboratory have shown that in dying thymocytes the expression of Tgm2 is induced by external signals derived from engulfing macrophages, such as retinoids, transforming growth factor (TGF)-β and adenosine, the latter triggering the adenylate cyclase signaling pathway. The existence of TGF-β and retinoid responsive elements in the promoter region of Tgm2 has already been reported, but the intergenic regulatory elements participating in the regulation of Tgm2 have not yet been identified. Here we used publicly available results from DNase I hypersensitivity analysis followed by deep sequencing and chromatin immunoprecipitation followed by deep sequencing against CCCTC-binding factor (CTCF), H3K4me3, H3K4me1 and H3K27ac to map a putative regulatory element set for Tgm2 in thymocytes. By measuring eRNA expressions of these putative enhancers in retinoid, rTGF-β or dibutiryl cAMP-exposed thymocytes we determined which of them are functional. By applying ChIP-qPCR against SMAD4, retinoic acid receptor, retinoid X receptor, cAMP response element binding protein, P300 and H3K27ac under the same conditions, we identified two enhancers of Tgm2, which seem to act as integrators of the TGF-β, retinoid and adenylate cyclase signaling pathways in dying thymocytes. Our study describes a novel strategy to identify and characterize the signal-specific functional enhancer set of a gene by integrating genome-wide datasets and measuring the production of enhancer specific RNA molecules.

Original languageEnglish
Pages (from-to)964-974
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1859
Issue number8
DOIs
Publication statusPublished - Aug 1 2016

Fingerprint

Retinoids
Thymocytes
Transforming Growth Factors
Genes
High-Throughput Nucleotide Sequencing
Adenylyl Cyclases
Retinoid X Receptors
Cyclic AMP Response Element-Binding Protein
Retinoic Acid Receptors
Macrophages
Deoxyribonuclease I
Biological Phenomena
Genetic Promoter Regions
Adenosine
Chromatin Immunoprecipitation
Chromatin
RNA
Apoptosis
Hypersensitivity
Molecules

Keywords

  • Apoptosis
  • ChIP-seq
  • Enhancer RNA
  • Gene regulation
  • T cells
  • Transglutaminase 2

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Transcriptional control of transglutaminase 2 expression in mouse apoptotic thymocytes. / Sándor, Katalin; Daniel, Bence; Kiss, Bea; Kovács, Fruzsina; Szondy, Z.

In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, Vol. 1859, No. 8, 01.08.2016, p. 964-974.

Research output: Contribution to journalArticle

Sándor, Katalin ; Daniel, Bence ; Kiss, Bea ; Kovács, Fruzsina ; Szondy, Z. / Transcriptional control of transglutaminase 2 expression in mouse apoptotic thymocytes. In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. 2016 ; Vol. 1859, No. 8. pp. 964-974.
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