Structure and expression of the hairless gene of mice.

Cachón‐González, M. Begoña; Fenner, Sabine; Coffin, John M.; Moran, Chris; Best, Steve; Stoye, Jonathan P.

doi:10.1073/pnas.91.16.7717

Cited by 168 publications

(167 citation statements)

References 37 publications

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“…1). The gene was identified as the responsible gene for the mouse mutant hairless (Cachon-Gonzalez et al, 1994). The hairless mouse was first recognized in 1926 for its characteristic hair loss phenotype, in which initial hair growth is normal, but after shedding, the hair does not grow back (Brooke, 1926), suggesting abnormalities in hair follicle regeneration.…”

Section: Hairlessmentioning

confidence: 99%

Roles of jumonji and jumonji family genes in chromatin regulation and development

Takeuchi

Watanabe

Takano-Shimizu

et al. 2006

Developmental Dynamics

177

148

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The jumonji (jmj) gene was identified by a mouse gene trap approach and has essential roles in the development of multiple tissues. The Jmj protein has a DNA binding domain, ARID, and two conserved jmj domains (jmjN and jmjC). In many diverse species including bacteria, fungi, plants, and animals, there are many jumonji family proteins that have only the jmjC domain or both jmj domains. Recently, Jmj protein was found to be a transcriptional repressor. Several proteins in the jumonji family are involved in transcriptional repression and/or chromatin regulation. Most recently, one of the human members has been shown to be a histone demethylase, and the jmjC domain is essential for the demethylase activity. Meanwhile, more and more evidence indicating that the jumonji family proteins play important roles during development is accumulating. Many proteins in the jumonji family may regulate chromatin and gene expression, and control development through various signaling pathways. Here, we highlight the roles of jmj and jumonji family proteins in chromatin regulation and development. Developmental Dynamics 235: 2449 -2459, 2006.

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Section: Hairlessmentioning

confidence: 99%

Roles of jumonji and jumonji family genes in chromatin regulation and development

Takeuchi

Watanabe

Takano-Shimizu

et al. 2006

Developmental Dynamics

177

148

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“…Genomic fragments from the hr gene were digested with frequent-cutting restriction enzymes, then incubated with 35 S-labeled thyroid hormone receptor (TR) in the absence (Left) or presence (Right) of unlabeled retinoid X receptor (RXR). Positions of genomic fragments are shown relative to the published mouse hr genomic structure (13). DNA used for binding reactions: -DNA, no DNA; BS, Bluescript; NK6, 6-kb NotI-KspI genomic fragment from hr; NK9, 9-kb NotI-KspI genomic fragment from hr; ⌬SV-CAT, negative control plasmid; TRE-CAT, positive control plasmid.…”

Section: Fig 1 Hr Is Directly Regulated By Thyroid Hormone (A)mentioning

confidence: 99%

“…The hr gene is expressed predominantly in skin and brain; the mutant phenotype in skin is progressive hair loss and increased susceptibility to cancer, while the neurological phenotype has not yet been described (11,13). The hr gene encodes a putative protein of approximately 127 kDa that lacks homology to known structural motifs other than a cluster of cysteine residues proposed to form a zinc finger (13). Toward defining the function of the hr gene product (Hr), we identified proteins that interact with Hr.…”

mentioning

confidence: 99%

The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors

Thompson

Bottcher

1997

Proc. Natl. Acad. Sci. U.S.A.

129

106

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Thyroid hormone is a critical mediator of central nervous system (CNS) development, acting through nuclear receptors to modulate the expression of specific genes. Transcription of the rat hairless (hr) gene is highly upregulated by thyroid hormone in the developing CNS; we show here that hr is directly induced by thyroid hormone. By identifying proteins that interact with the hr gene product (Hr), we find that Hr interacts directly and specifically with thyroid hormone receptor (TR)-the same protein that regulates its expression. Unlike previously described receptorinteracting factors, Hr associates with TR and not with retinoic acid receptors (RAR, RXR). Hr can act as a transcriptional repressor, suggesting that its interaction with TR is part of a novel autoregulatory mechanism.Many factors, both genetic and environmental, contribute to the formation and function of the mammalian central nervous system (CNS). An essential component of these processes is thyroid hormone (TH); if thyroid hormone levels are perturbed, abnormal development ensues, resulting in neurological deficits that include severe mental retardation (1-4). The effects of TH are mediated through the action of specific nuclear receptor proteins (5, 6). Thyroid hormone receptors (TR) act by binding to specific DNA sequences and subsequently activating or repressing the transcription of nearby genes in response to hormone binding (7,8). Several proteins that interact with TR and other nuclear hormone receptors, including both coactivators and corepressors, have been identified (9, 10).Although much is known about the mechanism of action of TR and other nuclear receptors, far less is known about the genes regulated by these receptors. We have shown that the rat hairless (hr) gene is highly up-regulated (Ͼ10-fold) by thyroid hormone in developing brain (11). The rapid induction (Ͻ4 hr) occurs even in the absence of protein synthesis, suggesting that hr is directly regulated by TR. Direct target genes are particularly important because such genes likely constitute the first step in the genetic program responsible for TH-mediated aspects of neural development. We show here that the upstream regulatory region of the hr gene includes a potent thyroid hormone response element (TRE), indicating that hr is indeed a direct target of TR.The murine hr locus was originally identified as a spontaneous mutation caused by an endogenous retrovirus (12). The hr gene is expressed predominantly in skin and brain; the mutant phenotype in skin is progressive hair loss and increased susceptibility to cancer, while the neurological phenotype has not yet been described (11, 13). The hr gene encodes a putative protein of approximately 127 kDa that lacks homology to known structural motifs other than a cluster of cysteine residues proposed to form a zinc finger (13). Toward defining the function of the hr gene product (Hr), we identified proteins that interact with Hr. Surprisingly, we found that Hr interacts with TR. Previously identified proteins that interact wit...

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“…The protein codified by this gene is a transcriptional corepressor for thyroid hormone receptors [13]. This gene is highly expressed in the brain and skin [1,4]. In its absence, hair follicles disintegrate and new hair is not induced [12].…”

Section: Introductionmentioning

confidence: 99%

“…In its absence, hair follicles disintegrate and new hair is not induced [12]. Cachon-Gonzalez et al [4] described the gene expression in mice, and amplified the entire cDNA of the gene, which consists of 19 exons with a coding sequence of 3750 nucleotides.…”

Section: Introductionmentioning

confidence: 99%

The hairless (hr) gene is involved in the congenital hypotrichosis of Valle del Belice sheep

Finocchiaro¹,

Portolano²,

Damiani

et al. 2003

Genet. Sel. Evol.

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-Congenital hypotrichosis in mammalian species consists of partial or complete absence of hair at birth. The hairless gene is often responsible for this disorder in men, mice and rats. Recent experimental data on Valle del Belice sheep reared in Sicily for milk production, support the genetic control of the ovine hypotrichosis as a Mendelian recessive trait. The ovine hairless gene was chosen as the candidate gene involved in this disorder. Blood samples were collected from Valle del Belice sheep with the normal and hypotrichotic phenotypes. Almost the entire hairless gene was successfully amplified using the long PCR technique. Unrelated sheep with differing phenotypes were randomly chosen for sequencing the amplified products. Different mutations related to the hypotrichotic phenotype were found in exon 3. In fact, sequencing revealed an A/T transversion at position 739, a G/A transition at position 823, and a C/T transition at position 1312. From these nucleotide exchanges, three substitutions of the processed mature protein were deduced at the amino acid positions 247 (Thr/Ser), 275 (Ala/Thr), and 438 (Gln/Stop). A PCR-SSCP based test was developed in order to detect the last mutation, which is responsible for the hypotrichotic phenotype.hairless gene / congenital hypotrichosis / ovine / Valle del Belice sheep

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Structure and expression of the hairless gene of mice.

Cited by 168 publications

References 37 publications

Roles of jumonji and jumonji family genes in chromatin regulation and development

Roles of jumonji and jumonji family genes in chromatin regulation and development

The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors

The hairless (hr) gene is involved in the congenital hypotrichosis of Valle del Belice sheep

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