XB-ART-50704Cell Biosci January 1, 2014; 4 73.
Epigenetic regulation of thyroid hormone-induced adult intestinal stem cell development during anuran metamorphosis.
Epigenetic modifications of histones are emerging as key factors in gene regulation by diverse transcription factors. Their roles during vertebrate development and pathogenesis are less clear. The causative effect of thyroid hormone (T3) on amphibian metamorphosis and the ability to manipulate this process for molecular and genetic studies have led to the demonstration that T3 receptor (TR) is necessary and sufficient for Xenopus metamorphosis, a process that resembles the postembryonic development (around birth) in mammals. Importantly, analyses during metamorphosis have provided some of the first in vivo evidence for the involvement of histone modifications in gene regulation by TR during vertebrate development. Furthermore, expression and functional studies suggest that various histone modifying epigenetic enzymes likely participate in multiple steps during the formation of adult intestinal stem cells during metamorphosis. The similarity between intestinal remodeling and the maturation of the mammalian intestine around birth when T3 levels are high suggests conserved roles for the epigenetic enzymes in mammalian adult intestinal stem cell development and/or proliferation.
PubMed ID: 25937894
PMC ID: PMC4417507
Article link: Cell Biosci
Genes referenced: dot1l hdac3 ncor1 prmt1
Article Images: [+] show captions
|Figure 1. T3-dependent intestinal remodeling during Xenopus metamorphosis involves larval cell apoptosis and de novo formation of adult epithelial stem cells. Xenopus undergoes a biphasic development. Its embryogenesis, when there is little TR or T3, leads to the formation of a free-living premetamorphic tadpoles by stage 45. During premetamorphosis (stage 45–54), there are high levels of TR but little T3, and the intestine has a simple structure with only a single fold, the typhlosole. During metamorphosis, the T3 level in the plasma rises to peak around stage 62, and most larval epithelial cells in the intestine undergo apoptosis, as indicated by the circles. Concurrently, the proliferating adult progenitor/stem cells are formed de novo from larval epithelial cells through dedifferentiation, as indicated by black dots. By the end of metamorphosis (stage 66), the levels of both TR and T3 drop lower and the newly differentiated adult epithelial cells in the intestine form a multiply folded epithelium.|
|Figure 2. Upregulation of genes involved in epigenetic modifications during intestinal stem cell development. (A) HDAC activity. Intestinal protein extracts were prepared from Xenopus laevis tadpoles at different stages and assayed for HDAC activity in the presence or absence of 10 nM TSA, an HDAC inhibitor. Means +/- SEMs are given. Statistical significance as compared with the stage 54 animals is expressed as *: P <0.01. Note that the HDAC-specific drug TSA inhibited all activities. See  for details. (B)-(D). The relative mRNA levels of N-CoR (B), PRMT1 (C), and Dot1L (D). The mRNA levels were determined by using total RNA from intestine at different stages during Xenopus laevis development. See [76, 87, 98] for details.|
|Figure 3. TSA induces direct TR target genes but blocks the regulation of late T 3 -response genes in premetamorphic tadpole intestine. Stage 55 tadpoles were treated with T3 (5 nM) and/or TSA (100 nM) for the indicated number of days. Total RNA was extracted from isolated intestine and assayed by PCR for the mRNA levels of indicated genes. IFAPB: intestinal fatty acid binding protein. See  for details.|
References [+] :
Bagamasbad, A role for basic transcription element-binding protein 1 (BTEB1) in the autoinduction of thyroid hormone receptor beta. 2008, Pubmed, Xenbase