Extinction of growth hormone expression in somatic cell hybrids involves repression of the specific trans-activator GHF-1

McCormick, Alison A.; Wu, David J.; Castrillo, José Luis; Dana, Sharon L.; Strobl, Jeannine S.; Thompson, E. Brad; Karin, Michael

doi:10.1016/0092-8674(88)90061-x

Cited by 88 publications

(56 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of extinction hasalso been investigated in hybrids between fibroblasts and pituitary cells, lymphoid cells, or hepatoma cells expressing growth hormone, immunoglobulin genes, or albumin, respectively. In those hybrids the transcription rate or mRNA level of a tissuespecific transcription factor required for expression of these genes (GHF-1, OCT2, or HNFl, respectively) was down-regulated (McCormick et al, 1988;Junker et al, 1988;Bergman et al, 1990;Junker et al, 1990;Cereghini et al, 1990). Extinction can also be mediated by activation of silencer-like target sequences (Triputti et al, 1988;Zaller et al, 1988;Yu et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-Dependent protein kinase

Boshart

Weih

Nichols

et al. 1991

Cell

180

100

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-Dependent protein kinase

Boshart

Weih

Nichols

et al. 1991

Cell

180

100

View full text Add to dashboard Cite

“…Among the different phenotypes that appear after fusion, extinction of specific cellular functions is most frequently observed (12). Previous studies utilizing several different hybrid cell systems, notably the pituitary cell x fibroblast, B-cell x fibroblast, and hepatoma x fibroblast hybrids, have analyzed the extinction of tissue-specific gene expression of growth hormone, immunoglobulin, otl-antitrypsin, and albumin, respectively (2,3,8,10,26,36,56,59). These studies concentrated on assessing the expression of transcription factors known to play a pivotal role in expression of the above-mentioned tissue-specific genes.…”

Section: Discussionmentioning

confidence: 99%

Extinction of Oct-3/4 gene expression in embryonal carcinoma x fibroblast somatic cell hybrids is accompanied by changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream region.

Ben-Shushan¹,

Pikarsky²,

Klar³

et al. 1993

Mol. Cell. Biol.

View full text Add to dashboard Cite

In this study we evaluate, for the first time, the molecular mechanism that underlies the extinction of a tissue-specific transcription factor, Oct-3/4, in somatic cell hybrids and compared it with its down-regulation in retinoic acid (RA)-treated embryonal carcinoma (EC) cells. The Oct-3/4 gene, which belongs to the POU family of transcription factors and is abundantly expressed in EC (OTF9-63) cells, provides an excellent model system with which to study the extinction phenomenon. Unlike other genes whose expression has been repressed in hybrid cells but not during in vivo differentiation, Oct-3/4 expression is dramatically repressed in OTF9-63 x fibroblast hybrids and also during embryogenesis. The ectopic expression of Oct-3/4 in hybrid cells under a constitutive promoter is sufficient for transcriptional activation of an octamer-dependent promoter. These results argue against the possibility that fibroblasts contain a direct repressor which binds directly to the octamer sequence and prevents Oct-3/4 protein from binding. The extinction of Oct-3/4 binding activity in the hybrid cells occurs at the level of mRNA transcription, similarly to the repression of Oct-3/4 transcription during in vivo differentiation. This shutdown of Oct-3/4 transcription in hybrid cells and in RA-treated EC cells is accompanied by de novo methylation of its 1.3-kb upstream region. In contrast to EC cells, in which this region is sensitive to MspI digestion, in hybrid cells and in RA-treated EC cells, the Oct-3/4 upstream region is resistant to MspI digestion, which suggests a change in its chromatin structure. Furthermore, extinction is not restricted to the endogenous Oct-3/4 gene but is also exerted upon a transiently transfected reporter gene driven by the Oct-3/4 upstream region. Thus, changes in the cellular activity of trans-acting factors acting on the upstream region also contribute to the inability of the hybrid and RA-treated EC cells to generate Oct-3/4 transcripts. In conclusion, this study draws a connection between the shutdown of Oct-3/4 expression in RA-differentiated EC cells and its extinction in hybrid cells. In both systems, repression of Oct-3/4 expression is achieved through changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream regulatory region.

show abstract

“…Recently, it has been shown that the B-cell-specific transcription of immunoglobulin genes is determined by a lymphoid-specific octamer-binding protein (Staudt et al 1986(Staudt et al , 1988Wirth et al 1987;Mfiller et al 1988) and that the erythrocytespecific regulation of globin genes depends, at least in part, on the erythroid-specific factor NF-E1 (Evans et al 1988;Galson and Housman 1988;Reitman and Felsenfeld 1988;Superti-Furga et al 1988;Wall et al 1988). A third interesting case is the pituitary-specific transcription factor GHF-1 (also referred to as Pit-l), which regulates a set of genes, including the growth hormone gene, that apparently are responsible for the cellular phenotype of the anterior pituitary (Bodner et al 1988;Ingraham et al 1988;McCormick et al 1988). Here, we have characterized a tissue-specific transcription factor of the sea urchin that may also be a master regulator of a family of genes that are all expressed in the same celltype-specific manner as the late H2A-2 and H2B-2 genes during sea urchin ontogeny.…”

Section: Developmental and Tissue-specific Regulation Of Tsapmentioning

confidence: 99%

Developmental and tissue-specific regulation of a novel transcription factor of the sea urchin.

Barberis

Superti‐Furga²,

Vitelli³

et al. 1989

Genes Dev.

View full text Add to dashboard Cite

We have identified a novel transcription factor that interacts with the promoter of four tissue-specific late histone H2A-2 and H2B-2 genes of the sea urchin by DNase I footprint, mobility shift, and methylation interference analyses. The binding site for this factor is required for efficient transcription of the H2B-2.1 gene both in vitro in nuclear extracts of gastrula embryos and in vivo in microinjected sea urchin embryos. This factor binds with equal affinity to the recognition sequences of all four histone genes in cross-competition assays. Moreover, the binding site of the H2B-2.2 promoter can functionally substitute for that of the H2B-2.1 gene in in vivo expression experiments. Nevertheless, all four binding sites share little sequence homology with each other. This transcription factor increases in abundance during embryogenesis and has been detected in the adult sea urchin only in the tube feet, where the late H2A-2 and H2B-2 genes are expressed specifically. Therefore, we refer to this factor as tissue-specific activator protein (TSAP). The close correlation between the presence of TSAP and the expression pattern of the late H2A-2 and H2B-2 genes suggests that this transcription factor is directly responsible for the developmental and tissue-specific regulation of these genes.

show abstract

Extinction of growth hormone expression in somatic cell hybrids involves repression of the specific trans-activator GHF-1

Cited by 88 publications

References 38 publications

The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-Dependent protein kinase

The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-Dependent protein kinase

Extinction of Oct-3/4 gene expression in embryonal carcinoma x fibroblast somatic cell hybrids is accompanied by changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream region.

Developmental and tissue-specific regulation of a novel transcription factor of the sea urchin.

Contact Info

Product

Resources

About