Chromatin transcriptionally repressive state

A system such as this can provide a powerful mechanism for transcriptional control. While bound to nucleosomes, PARP-1 promotes a transcriptionally repressed state, but one that is simultaneously poised for activation because of the allosteric activating effect of nucleosomes on PARP-1 enzymatic activity. In the presence of NAD+, PARP-1 can autoPARylate and release from nucleosomes, shifting the chromatin to a more transcriptionally active conformation. PARC can reset the system by cleaving the PAR chains from PARP-1, allowing PARP-1 to re-bind the nucleosomes and re-establish a transcriptionally repressed state. 

The expression of a somatic form of histone HI could constitute one component of the transcriptionally repressive state. The biogenesis of a mature nucleosome is associated with the formation of transcriptionally repressive chromatin. While the association of DNA with histones H3 and H4 can generate a nucleosomelike structure, the DNA can still readily interact with transcription factors. This ability is diminished with the further incorporation of histones H2A and H2B that results in the formation of a nucleosome that can exclude the binding of basic components of the transcription machinery (e.g., RNA polymerase II). The formation of a truly transcriptionally repressive chromatin structure is brought about by the addition of histone HI, which can be incorporated only after the addition of histones H2A and H2B and causes chromatin to condense into a 30-nm fiber (Bouvet et al., 1994). The requirement for an enhancer for efficient promoter utilization in zygotic nuclei, but not the pronuclei, could reflect the developmental acquisition of chromatin con-... 

In summary, the reciprocal decrease in histone acetylation coupled with an increase in histone HI expression could, in principle, promote the conversion of transcriptionally permissive chromatin into a transcriptionally repressed form and hence serve as the foundation for the development of the transcriptionally repressed state that is first observed at the two-cell stage. The second round of DNA replication may also contribute to the development of this state by displacing transcriptionally productive complexes and thus providing an opportunity for the assembly of a mature, transcriptionally repressive chromatin structure. 

Fig. 1.40. Model of repression and activation of transcription. The figure illustrates various mechanisms of repression of transcription, a) genes are in a generally repressed states in inactive chromatin. In a first phase of activation the chromatin is restrnctured. b) The promoter is now accessible for the binding of the basal transcription factors and for RNA polymerase II. c) An initiation complex is formed that contains the central components of the transcription apparatns, bnt which enables transcription only at a low rate, d) the binding of repressors to the transcription initiation complex can prevent fnrther activation of transcription at this step, e) the binding of transcription activators to their DNA elements leads to activation of transcription, f) an active repression is affected by proteins that bind seqnence specifically to DNA elements and in their DNA-bound form inhibit the transcritption preventing interactions with the transcription apparatus.

The amino terminal tads of the four core histones contain lysines that are acetylated by HATs and deacetylated by HDACs. The histone octamer (H2A, H2B, H3, H4)2 is represented as a cylinder wrapped by DNA. It is thought that neutrahzation of the positive charges on the histone tads results in alterations of the nucleosome structure that may lead to a higher mobdity of the nucleosome and/or an improved accessibdity of the bound DNA, with accompanying changes in chromatin structure, chromatin hierarchy and transcription. In most, but not ad cases, deacetylation correlates with the repressed state and acetylation correlates with the transcriptionady active state. 

In the case of the T3R and RAR specific repressor proteins have been identified which bind to the receptor and mediate an inhibition of transcription (Hoerlein et al, 1995). The repressor proteins are also termed co-repressors Among the repressors are found proteins with histone deacetylase activity (see 1.4.6). The RXR heterodimers possibly stabilize the repressed state of chromatin by recruiting a histone deacetylase to the chromatin. 

Fig. 1.32 Pathways of repression of transcription. The figure illustrates various mechanisms of repression of transcription, a) Repressors can induce a generally repressed state in chromatin which is incompatible with transcription. To allow transcription at all, the repressed state must be relieved, b) Repressors can target the transcription complex...

Fig. 4.11 Model of repression and activation of T3R. In the absence of the T3 hormone, a hetero-dimeric RXR-T3R receptor is bound at the T3-re-sponsive element,TRE, establishing a basal repressed state. The repressed state is maintained by recruitment of corepressor complexes containing histone deacetylase activity. X refers to potential unidentified cofactors (possibly chromatin remodeling complexes or SRBs) which help to keep the promotor-bound basal transcription apparatus in...

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