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1.
Mol Cell Biol ; 20(18): 6627-37, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10958660

RESUMO

The histone H1(0)-encoding gene is expressed in vertebrates in differentiating cells during the arrest of proliferation. In the H1(0) promoter, a specific regulatory element, which we named the H4 box, exhibits features which implicate a role in mediating H1(0) gene expression in response to both differentiation and cell cycle control signals. For instance, within the linker histone gene family, the H4 box is found only in the promoters of differentiation-associated subtypes, suggesting that it is specifically involved in differentiation-dependent expression of these genes. In addition, an element nearly identical to the H4 box is conserved in the promoters of histone H4-encoding genes and is known to be involved in their cell cycle-dependent expression. The transcription factors interacting with the H1(0) H4 box were therefore expected to link differentiation-dependent expression of H1(0) to the cell cycle control machinery. The aim of this work was to identify such transcription factors and to obtain information concerning the regulatory pathway involved. Interestingly, our cloning strategy led to the isolation of a retinoblastoma protein (RB) partner known as HBP1. HBP1, a high-mobility group box transcription factor, interacted specifically with the H1(0) H4 box and moreover was expressed in a differentiation-dependent manner. We also showed that the HBP1-encoding gene is able to produce different forms of HBP1. Finally, we demonstrated that both HBP1 and RB were involved in the activation of H1(0) gene expression. We therefore propose that HBP1 mediates a link between the cell cycle control machinery and cell differentiation signals. Through modulating the expression of specific chromatin-associated proteins such as histone H1(0), HBP1 plays a vital role in chromatin remodeling events during the arrest of cell proliferation in differentiating cells.


Assuntos
Regulação da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/metabolismo , Histonas/genética , Proteínas Repressoras/metabolismo , Proteína do Retinoblastoma/metabolismo , Adulto , Animais , Sequência de Bases , Diferenciação Celular , DNA Complementar , Proteína HMGB1 , Proteínas de Grupo de Alta Mobilidade/genética , Humanos , Camundongos , Dados de Sequência Molecular , Ratos , Sequências Reguladoras de Ácido Nucleico , Proteínas Repressoras/genética , Células Tumorais Cultivadas
2.
Gene ; 163(2): 227-32, 1995 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-7590271

RESUMO

In comparing several histone H1 promoters, we have identified a highly conserved sequence element, 5'-TGTGTTA, located approx. 450-480 bp upstream from the cap site. This TG-box is a near perfect inverted repeat of the previously characterized AC-box (5'-AAACACA). The distance between these elements is also highly conserved. We performed transient transfection assays with cat gene reporter constructs which indicated that both the presence and correct position of the TG-box were essential for maximal expression of the chicken 02 H1 promoter. To the best of our knowledge, this study represents the first demonstration of an effect by the TG-box on transcription of a major histone-encoding H1 gene.


Assuntos
Genes Homeobox , Histonas/genética , Transcrição Gênica , Animais , Sequência de Bases , Galinhas , Técnicas de Transferência de Genes , Dados de Sequência Molecular , Regiões Promotoras Genéticas/genética , Alinhamento de Sequência
3.
Immunity ; 6(2): 175-85, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9047239

RESUMO

Interleukin-3 (IL-3) is a cytokine that is expressed primarily in activated T cells. Here we identified an inducible T cell-specific enhancer 14 kb upstream of the IL-3 gene that responded to activation of T cell receptor signaling pathways. The IL-3 enhancer spanned an inducible cyclosporin A-sensitive DNase I-hypersensitive site found only in T cells. Four NFAT-like elements exist within the enhancer. The two most active NFAT-like elements were located at the center of the DNase I-hypersensitive site. One of these NFAT-like elements encompassed overlapping Oct- and NFATp/c-binding sites, which functioned in a highly synergistic manner. We suggest that the T cell-specific expression of the IL-3 gene is partly controlled through the enhancer by cooperation between Oct and NFAT family proteins.


Assuntos
Proteínas de Ligação a DNA/farmacologia , Desoxirribonuclease I/farmacologia , Elementos Facilitadores Genéticos/imunologia , Regulação da Expressão Gênica/imunologia , Proteínas de Homeodomínio/farmacologia , Interleucina-3/genética , Proteínas Nucleares , Linfócitos T/metabolismo , Fatores de Transcrição/farmacologia , Sequência de Bases , Ciclosporina/toxicidade , Sinergismo Farmacológico , Elementos Facilitadores Genéticos/efeitos dos fármacos , Células HeLa , Fator C1 de Célula Hospedeira , Humanos , Células Jurkat , Dados de Sequência Molecular , Fatores de Transcrição NFATC , Fator 1 de Transcrição de Octâmero , Fator 2 de Transcrição de Octâmero
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