Repression Indirect

Fig. 4. Domain structure of mammalian DNA methyltransferases. (a) The domain structure of the known DNA methyltransferases, depicting the conserved catalytic domain (dark box) and other identified domains. Conserved aminoacid motifs in the catalytic domain are shown in lighter shade of gray. (b) Schematic representation of the reported protein-protein interactions of Dnmtl with a number of regulatory proteins interactions that modulate Dnmtl methyitransferase activity (darker rectangles) or mediate methylation-independent transcriptional repression mechanisms (lighter rectangles). When Dnmtl represses transcription through its enzymatic activity, it has been described to interact with some proteins PCNA [37] and an oncogenic transcription factor PML-RAR [25]. Note that in the case of the PML-RAR transcription factor, histone deacetylase 1 (HDACl) is also bound to the complex. When Dnmtl represses transcription via methylation-independent pathways, it binds to HDACs either directly [34] or indirectly through other proteins the corepressor DMAPl [33], the retinoblastoma protein, and a gene-specific transcription factor [31].

The expression of several genes is induced or repressed by hemopexin-mediated heme transport. Most of these are simple responses of the cell to the increased heme (or iron derived from heme) in the cell. For example, HO-1 is induced (15, 88), ferritin levels rise (14, 61, 89), the transferrin receptor is down-regulated (15), and hemopexin mRNA itself is induced (A. Smith, unpublished). However, MT-1 is also induced, apparently to prepare the cell for oxidative stress thus, in addition to sequestering heme in a low-spin, non-oxidatively active form, hemopexin also indirectly exerts antioxidant effects by inducing MT-1 (16, 61, 90). 

Specific repressors can exert their influence directly or indirectly. Indirect repression is, for example, if a repressor protein competes with transcriptional activators for the binding site on the promoter. The extent of repression is then determined by the relative affinity of both proteins to the DNA element and their concentration ratios. The DNA-bound repressor in this case does not act as a transcriptional activator. 

A further possibility for indirect repression results from heterodimerization (see 1.4.4.3). Heterodimers between two transcription factors, in which one of the partners possesses a DNA-binding domain with weak affinity, can inactivate a transcriptional activator in a heterodimer complex. Since a strong binding to the DNA element usually requires both subimits of a DNA-binding protein, transcription activation by this type of heterodimer is not possible. 

A complicated and indirect interaction of the mitosis specific activation of the Pj-responsive gene PH05 and the PolyP level in S. cerevisiae has been found (Neef and Kladde, 2003). PH05 mitotis activation was repressed by Pj addition, which significantly... 

It may be particularly hard for you to bring up information and feelings about repressed material, even if you are practicing the systematic type of self-observation that will be discussed in Chapter 17. By definition, there is a powerful reason why the material is being blocked from consciousness, and the desire to know yourself through self-observation may not be sufficient to overcome this block. You may become sensitive to peculiar reactions at times, the indirect effects of repression, like our patient s angry tone of voice that was so much at variance with his statement that he loved his mother but it may take outside intervention, from a therapist or teacher, to help you uncover repressed material. 

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