Demethylation in the 5′‐flanking region of mouse cellular retinoic acid binding protein‐I gene is associated with its high level of expression in mouse embryos and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells

Wei, Li‐Na; Lee, Chih‐Hao ‐H

doi:10.1002/aja.1002010102

Cited by 23 publications

(19 citation statements)

References 31 publications

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“…The promoter of the human CRABP1 gene has not been characterized. Evidence from the mouse Crabp1 gene suggests that DNA methylation might play a role in regulating the expression of this gene 40. We used the WebGene computer program (http://www.itba.mi.cnr.it/webgene/) to identify CpG islands surrounding the translation initiation site of human CRABP1 .…”

Section: Resultsmentioning

confidence: 99%

Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma

Huang

Chapelle

Pellegata

2003

Intl Journal of Cancer

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We previously obtained gene expression profiles of 8 matched papillary thyroid carcinoma (PTC) and normal tissues using DNA microarrays. To identify novel tumor suppressor genes involved in thyroid carcinogenesis, we here analyze genes showing lower expression in PTC tumors than in normal thyroid tissues. A search for loss of heterozygosity (LOH) in 49 regions that harbor consistently down-regulated genes revealed LOH in only 4 regions and in just a very small number of tumors. To determine whether the underexpression might be due to promoter methylation, we used combined bisulfite restriction analysis and bisulfite sequencing to study 7 underexpressed genes. Loss of expression of MT1G and CRABP1 is accompanied by hypermethylation in the 5 regions of these genes, but methylation was not seen in other genes tested. Combined treatment with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine (5-Aza-dC) and the histone deacetylase inhibitor trichostatin A (TSA) resulted in demethylation and re-expression of the MT1G gene in the cell line K2. Treatment with 5-Aza-dC alone restored CRABP1 expression in a colorectal cancer cell line, SW48. In conclusion, LOH is a remarkably rare mechanism of loss of gene function in PTC. In contrast, hypermethylation of promoter CpG islands seems to occur at higher frequency. MT1G and CRABP1 are novel genes that are likely involved in the pathogenesis of sporadic PTC.

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Section: Resultsmentioning

confidence: 99%

Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma

Huang

Chapelle

Pellegata

2003

Intl Journal of Cancer

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“…Indeed, heterochromatin proteins 1α (HP1α) and 1γ (HP1γ) and histone H1 (H1) were increasingly recruited to this promoter, and so was G9a, the H3K9 methyltransferase. The promoter of this gene is rich in clustered CpG islands and its repression is known to be related to the level of cytosine-methylation (39). Consistently, MeCP2 was increasingly detected on both TRE and GC box regions and RNA polymerase II (RPB1) gradually disappeared from this promoter in more differentiated cultures.…”

Section: Resultsmentioning

confidence: 99%

RIP140 in thyroid hormone-repression and chromatin remodeling of Crabp1 gene during adipocyte differentiation

Park¹,

Huang²,

Persaud³

et al. 2009

Nucleic Acids Research

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Cellular retinoic acid binding protein 1 (Crabp1) gene is biphasically (proliferation versus differentiation) regulated by thyroid hormone (T3) in 3T3-L1 cells. This study examines T3-repression of Crabp1 gene during adipocyte differentiation. T3 repression of Crabp1 requires receptor interacting protein 140 (RIP140). During differentiation, the juxtaposed chromatin configuration of Crabp1 promoter with its upstream region is maintained, but the 6-nucleosomes spanning thyroid hormone response element to transcription initiation site slide bi-directionally, with the third nucleosome remaining at the same position throughout differentiation. On the basal promoter, RIP140 replaces coactivators GRIP1 and PCAF and forms a repressive complex with CtBP1, HDAC3 and G9a. Initially active chromatin marks on this promoter, histone modifications H3-Ac and H3K4-me3, are weakened whereas repressive chromatin marks, H3K9-me3 and H3K27-me3 modification and recruitment of G9a, HP1α, HP1γ and H1, are intensified. This is the first study to examine chromatin remodeling, during the phase of hormone repression, of a bi-directionally regulated hormone target gene, and provides evidence for a functional role of RIP140 in chromatin remodeling to repress hormone target gene expression.

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“…However, the upstream regulator of its expression in normal and pathological conditions is unclear. During embryonic development, the crabp1 promoter is demethylated to induce gene expression in specific tissues [56], while in adult tissues, the promoter becomes inaccessible through chromatin modification to restrict its expression [57]. Crabp1 can be activated by thyroid hormone (T3/T4) binding of the holo-thyroid hormone receptors/retinoid receptors that in turn bind to the thyroid response element (TRE) located approximately 1 kb upstream of the crabp1 basal promoter.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-associated breast cancers are driven by differences in adipose stromal cells present during lactation

et al. 2014

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IntroductionThe prognosis of breast cancer is strongly influenced by the developmental stage of the breast when the tumor is diagnosed. Pregnancy-associated breast cancers (PABCs), cancers diagnosed during pregnancy, lactation, or in the first postpartum year, are typically found at an advanced stage, are more aggressive and have a poorer prognosis. Although the systemic and microenvironmental changes that occur during post-partum involution have been best recognized for their role in the pathogenesis of PABCs, epidemiological data indicate that PABCs diagnosed during lactation have an overall poorer prognosis than those diagnosed during involution. Thus, the physiologic and/or biological events during lactation may have a significant and unrecognized role in the pathobiology of PABCs.MethodsSyngeneic in vivo mouse models of PABC were used to examine the effects of system and stromal factors during pregnancy, lactation and involution on mammary tumorigenesis. Mammary adipose stromal cell (ASC) populations were isolated from mammary glands and examined by using a combination of in vitro and in vivo functional assays, gene expression analysis, and molecular and cellular assays. Specific findings were further investigated by immunohistochemistry in mammary glands of mice as well as in functional studies using ASCs from lactating mammary glands. Additional findings were further investigated using human clinical samples, human stromal cells and using in vivo xenograft assays.ResultsASCs present during lactation (ASC-Ls), but not during other mammary developmental stages, promote the growth of carcinoma cells and angiogenesis. ASCs-Ls are distinguished by their elevated expression of cellular retinoic acid binding protein-1 (crabp1), which regulates their ability to retain lipid. Human breast carcinoma-associated fibroblasts (CAFs) exhibit traits of ASC-Ls and express crabp1. Inhibition of crabp1in CAFs or in ASC-Ls abolished their tumor-promoting activity and also restored their ability to accumulate lipid.ConclusionsThese findings imply that (1) PABC is a complex disease, which likely has different etiologies when diagnosed during different stages of pregnancy; (2) both systemic and local factors are important for the pathobiology of PABCs; and (3) the stromal changes during lactation play a distinct and important role in the etiology and pathogenesis of PABCs that differ from those during post-lactational involution.

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Demethylation in the 5′‐flanking region of mouse cellular retinoic acid binding protein‐I gene is associated with its high level of expression in mouse embryos and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells

Cited by 23 publications

References 31 publications

Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma

Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma

RIP140 in thyroid hormone-repression and chromatin remodeling of Crabp1 gene during adipocyte differentiation

Pregnancy-associated breast cancers are driven by differences in adipose stromal cells present during lactation

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