Transcriptional complex expression

Through these examples, I wanted to illustrate the fact that the expression molecular description can have at least three different meanings. These three levels of representation are not independent. For instance, the atoms and bonds that make up the jaws of RNA polymerase II can be described, as well as RNA polymerase II can be integrated, with transcription factors and DNA, in the general picture of the preinitiation transcription complex. However, in order to answer a specific question, one particular level of description is always more significant, better adapted than others, with a greater explanatory value. 

Gene expression requires that chromatin be opened for access by transcription complexes (RNA polymerase and transcription factors, Chapter 5). Chromatin-modifyLi activities include ... 

The RB gene encodes a transcriptional co-repressor which forms a complex with the cell-cycle-regulating transcription factor E2F (members of the E2F family of transcriptional activators control the genes involved in the Gj/S transition and in DNA replication 20 see Chapter 12). The RB—E2F transcriptional complex contains additional factors, such as the histone deacetylase, HDACl, which facilitates access of the transcriptional complex to E2F-responsive gene promoters, such as the cycKn E promoter. pRB and HDACl act in concert and repress the cyclin E promoter. i Hence the retinoblastoma protein (pRB) is a tumour-suppressor that represses gene expression in concert with a histone deacetylase, by modulating the architecture of chromatin (Fig. 15.4). The pRB- E2F transcriptional complex also represses transcription of RNA polymerase III22 (see also Chapter 9). 

The general mechanism of receptor-mediated action of steroid hormones is very similar for each of the five classes. Briefly, the steroid enters the cell and binds to an intraceUnar protein. The resnlting receptor-steroid complex is converted in a poorly nn-derstood step called activation to a form that binds to specific, biologically active DNA seqnences (called hormone response elements, or HREs) of the nnclear chromatin. These HRE-bonnd receptor-steroid complexes recrnit various cofactors and then interact with the transcription complex containing RNA polymerase 11 to modify the rates of transcription of a nearby DNA sequence coding for an expressed protein (Fig. 2). This alteration of transcription rate is typically fast (15-30 min) (14). 

The inhibition of multifunctional enzymes can also have therapeutic interest. The 26S proteasome is a mul-ticatalytic intracellular protease complex expressed in eukaryotic cells. This complex is responsible for selective degradation of intracellular proteins that are responsible for cell proliferation, growth, regulation of apoptosis and transcription of genes. Thus, proteasome inhibition is a potential treatment option for cancer and diseases due to aberrant inflammation conditions. Bortezomib and PS-519 are the first proteasome inhibitors that have entered clinical trials. In multiple myeloma, both the FDA (United States... 

Retention of transcription factors in mitotic chromosomes could provide one component of this molecular memory. Immunocytochemical and subcellular fraction of mitotic Hela cells indicated that some TFIID remained associated with mitotic chromatin (Segil et al., 1996). Thus, upon entry into interphase, TFIID could nucleate the formation of a productive transcription complex for a gene expressed in G2 of the prior cell cycle. The retention of other transcription factors Or enhancer proteins could promote the same effect. 

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