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Hairless is a nuclear receptor corepressor essential for skin function.

Thompson CC - Nucl Recept Signal (2009)

Bottom Line: Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors.As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear.The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT.

View Article: PubMed Central - PubMed

Affiliation: Wyeth Research, Collegeville, Pennsylvania, USA. ThompsC5@wyeth.com

ABSTRACT
The activity of nuclear receptors is modulated by numerous coregulatory factors. Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors. As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear. The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT. Mutation of the Hr gene results in congenital hair loss in both mice and men. Investigation of Hairless function both in vitro and in mouse models in vivo has revealed a critical role in maintaining skin and hair by regulating the differentiation of epithelial stem cells, as well as a putative role in regulating gene expression via chromatin remodeling.

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Schematic representation of rat HR structural and functional domains.Repression domains (RD1, 236-450; RD2, 750-864; RD3, 864-981); TR-interacting domains (TR-ID1, 816-830; TR-ID2, 1026-1038); ROR-interacting domains, ROR-ID1, 586-590; ROR-ID2, 778-782); cysteine-rich domain, 587-712; JmjC domain, 964-1175. Note that rat HR is 1207 amino acids, mouse and human Hr initiate at an internal AUG (amino acid 27 in rat Hr) and are 1182 and 1189 amino acids, respectively.
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fig1: Schematic representation of rat HR structural and functional domains.Repression domains (RD1, 236-450; RD2, 750-864; RD3, 864-981); TR-interacting domains (TR-ID1, 816-830; TR-ID2, 1026-1038); ROR-interacting domains, ROR-ID1, 586-590; ROR-ID2, 778-782); cysteine-rich domain, 587-712; JmjC domain, 964-1175. Note that rat HR is 1207 amino acids, mouse and human Hr initiate at an internal AUG (amino acid 27 in rat Hr) and are 1182 and 1189 amino acids, respectively.

Mentions: Analysis of HR deletion derivatives expressed as fusion proteins with the GAL4 DNA binding domain revealed three domains capable of mediating repression [Potter et al., 2001]. Repression domains include a single amino terminal domain (amino acids 236-450; RD1), and two carboxyl terminal domains (amino acids 750-864, RD2; amino acids 864-981, RD3) (Figure 1). The functional organization differs from N-CoR and SMRT, as RD2 overlaps with a receptor interaction domain (see below).


Hairless is a nuclear receptor corepressor essential for skin function.

Thompson CC - Nucl Recept Signal (2009)

Schematic representation of rat HR structural and functional domains.Repression domains (RD1, 236-450; RD2, 750-864; RD3, 864-981); TR-interacting domains (TR-ID1, 816-830; TR-ID2, 1026-1038); ROR-interacting domains, ROR-ID1, 586-590; ROR-ID2, 778-782); cysteine-rich domain, 587-712; JmjC domain, 964-1175. Note that rat HR is 1207 amino acids, mouse and human Hr initiate at an internal AUG (amino acid 27 in rat Hr) and are 1182 and 1189 amino acids, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2807636&req=5

fig1: Schematic representation of rat HR structural and functional domains.Repression domains (RD1, 236-450; RD2, 750-864; RD3, 864-981); TR-interacting domains (TR-ID1, 816-830; TR-ID2, 1026-1038); ROR-interacting domains, ROR-ID1, 586-590; ROR-ID2, 778-782); cysteine-rich domain, 587-712; JmjC domain, 964-1175. Note that rat HR is 1207 amino acids, mouse and human Hr initiate at an internal AUG (amino acid 27 in rat Hr) and are 1182 and 1189 amino acids, respectively.
Mentions: Analysis of HR deletion derivatives expressed as fusion proteins with the GAL4 DNA binding domain revealed three domains capable of mediating repression [Potter et al., 2001]. Repression domains include a single amino terminal domain (amino acids 236-450; RD1), and two carboxyl terminal domains (amino acids 750-864, RD2; amino acids 864-981, RD3) (Figure 1). The functional organization differs from N-CoR and SMRT, as RD2 overlaps with a receptor interaction domain (see below).

Bottom Line: Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors.As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear.The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT.

View Article: PubMed Central - PubMed

Affiliation: Wyeth Research, Collegeville, Pennsylvania, USA. ThompsC5@wyeth.com

ABSTRACT
The activity of nuclear receptors is modulated by numerous coregulatory factors. Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors. As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear. The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT. Mutation of the Hr gene results in congenital hair loss in both mice and men. Investigation of Hairless function both in vitro and in mouse models in vivo has revealed a critical role in maintaining skin and hair by regulating the differentiation of epithelial stem cells, as well as a putative role in regulating gene expression via chromatin remodeling.

Show MeSH