Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2012 Mar 23;287(13):10039-50. doi: 10.1074/jbc.M111.335661. Epub 2012 Feb 7.

Thyroid hormone activates protein arginine methyltransferase 1 expression by directly inducing c-Myc transcription during Xenopus intestinal stem cell development.

Author information

1
Section on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, National Institutes of Health (NIH)), Bethesda, Maryland 20892, USA.

Abstract

Adult organ-specific stem cells are essential for organ homeostasis and tissue repair and regeneration. The formation of such stem cells during vertebrate development is poorly understood. Intestinal remodeling during thyroid hormone (T3)-dependent Xenopus metamorphosis resembles postembryonic intestinal maturation in mammals. During metamorphosis, the intestine is remodeled de novo via a yet unknown mechanism. Protein arginine methyltransferase 1 (PRMT1) is up-regulated in and required for adult intestinal stem cells during metamorphosis. PRMT1 up-regulation is the earliest known molecular event for the developing stem cells and is also conserved during zebrafish and mouse intestinal development. To analyze how PRMT1 is specifically up-regulated during the formation of the adult intestinal stem cells, we cloned the Xenopus PRMT1 promoter and characterized it in CaCo-2 cells, a human cell line with intestinal stem cell characteristics. Through a series deletion and mutational analyses, we showed that the stem cell-associated transcription factor c-Myc could bind to a conserved site in the first intron to activate the promoter. Furthermore, we demonstrated that during metamorphosis, both c-Myc and PRMT1 were highly up-regulated, specifically in the remodeling intestine but not the resorbing tail, and that c-Myc was induced by T3 prior to PRMT1 up-regulation. In addition, we showed that T3 directly activated the c-Myc gene during metamorphosis in the intestine via binding of the T3 receptor to the c-Myc promoter. These results suggest that T3 induces c-Myc transcription directly in the intestine, that c-Myc, in turn, activates PRMT1 expression, and that this is an important gene regulation cascade controlling intestinal stem cell development.

PMID:
22315222
PMCID:
PMC3323014
DOI:
10.1074/jbc.M111.335661
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center