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Index >> Regulation of Protein Synthesis - Operon >> Nonhistone Protein as Depressors

Nonhistone Protein as Depressors

Nonhistone Protein as Depressors

- Paul and co-workers (1971) have suggested a similar model, except that in their model gene specific acid proteins displace the histone.

The nonhistone chromosomal proteins have a number of characteristics expected of a regulatory protein with specific action.

(1) NHG proteins occur in a far greater variety of forms than histones.

They differ greatly in size and the length of the time they are associated with DNA before degradation.

(2) The pattern of NHC proteins varies from species to species. Even different tissues in the same organism differ in their NHC protein pattern.

(3) The pattern of NHC proteins varies with the developmental stage and also with the stage of the cell cycle.

Thus NHC proteins isolated from interphase cells, where transcription of RNA is maximal, differ from those isolated from metaphasic cells, where only a few genes transcribe RNA.

(4) NHC proteins have been localized in the active regions of the chromosomes.

(5) Inhibition of transcription caused by histones is reversed on addition of NHC proteins, i.e. NHC proteins act as derepressors.

(6) Moreover, this derepression has specificity. NHC proteins bind to specific gene loci.

This has been demonstrated as follows.

Chromatin isolated from rabbit thymus and bone marrow was dissociated into DNA; histones and NHC protein.

Reassociation of DNA and histones resulted in chromatin free from NHC protein.

No transcription of RNA was observed in such preparations.

RNA synthesis is completely suppressed by the histones.

However, addition of NHC proteins from bone marrow resulted in transcription of RNA with characteristics of that of bone marrow.

Similarly, addition of thymus NHC proteins resulted in RNA with characteristics of that found in thymus cells.

This shows that NHC proteins are specific for a cell type.

It is presumed that NHC proteins derepress specific genes and stimulate transcription of specific genetic regions.

In another test this specificity is even more clearly demonstrated.

Foetal mouse liver cells synthesize the protein globin (the non-iron part of haemoglobin) but foetal mouse brain cells do not. Iii vitro addition of NHC proteins from foetal liver to DNA and histone from the brain leads to production of globin mRNA.

(7) NHC proteins show preferential binding to the DNA of the organisms from which they are isolated.

According to the theory of Stein and his coworkers (see Stein, G.S., Stein J.S. and Kleinsmith, 1975), regulation of gene activity .

Histones probably act as nonspecific repressors of genetic function and prevent transcription of RNA from DNA. Individual NHC proteins recognize certain sites on DNA and hind to it there.

They then pull off the histone repressor from the site, thus derepressing DNA. NHC proteins act by derepressing.

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