the DNA at this point and displaces histone. 

 This leaves free just one strand to code for 

 messenger RNA. That's fine, but I find it dif- 

 ficult to understand how this process is reversed; 

 and also, it wasn't explained how he thought 

 hormones would stimulate this removal process. 

 Also he doesn't explain differential gene action 

 or epigenetic control. 



So, just for fun. Dr. Maurer and I present 

 another model. It is shown in Fig. 19. This has 

 at least the advantage, I think, of concentrating 

 thought on a dynamic model rather than a static 

 one, and I feel that it's a dynamic process that's 

 involved in repression. Now, firstof all, wehave 

 the genome of a differentiated tissue in which 

 some specific areas of this genome are com- 

 pletely unavailable for genetic transcription. 

 In the in vitro reconstitution experiments of 

 Bonner and Huang it was found that the histones 

 were virtually 100% efficient in cutting off 

 DNA- dependent RNA synthesis. So, we have 

 areas which are cut off with those histones; 

 they're not allowed to be transcribed, and, dur- 

 ing the lifetime of a particular DNA molecule, 

 there will be no RNA synthesis in these genes. 

 We have another basic protein; we haven't 

 specified any more than to say it's basic, and 

 based on the results of Huang and Bonner (14) 

 we postualte a basic protein-RNA linkage. Now, 

 if one wants to think of proteins linked to a 

 very special RNA like this, it would seem to 

 require a covalent linkage. Again we're specu- 



lating a little; we don't know that it is covalent, 

 but the evidence is beginning to mount up 

 toward that possibility. If that's so, these have 

 to be linked, presumably, through a series of 

 enzymic reactions. This material which we call 

 a functional repressor has the ability to recog- 

 nize a specific gene because of this RNA. It 

 is then possible to conceive of a dynamic 

 equilibrium in a section of the genome. We 

 suggest thinking along the lines of some sort 

 of dynamic equilibrium with the repressor going 

 on and the repressor falling off and being de- 

 graded. Now, if we postulate this dynamic sys- 

 tem, then it's possible to conceive of induction 

 acting by somehow inhibiting the linkage of 

 these two component parts in the formation of 

 the functional repressor. In this case, the re- 

 pressor is not formed, so the equilibrium will 

 shift away from the genome. Protein synthesis 

 malfunction would also give rise to a decrease 

 in the concentration of the repressor, as would 

 inhibition of RNA synthesis. Perhaps we can 

 begin the discussion with this model that we 

 have proposed. 



GROSS: How do you get the stable histones 

 which are not turning over? How is their speci- 

 ficity compared to the one which does? 



CHALKELY: Their synthesis would require 

 both spatial and apparently temporal specificity - 

 whether this synthesis is directed by messenger 

 RNA or by other methods is an interesting 

 problem. 



DYNAMIC MODEL FOR INDUCTION AND REPRESSION 



PROTEINSYNTHESIS 



RNA-SYNTHESIS 



c 



D 



BASIC PROTEIN 



I FORMATION OF REPRESSOR 



RNA 



INHIBITION OF FORMATION OF THE REPRESSOR 



FUNCTIONAL 

 REPRESSOR 



= INDUCTION 



I _Ji 



I FUNCTION OF REPRESSOR] i I REPRESSION] 



Z^OOOOOOOC 



DEGRADATION 

 OF REPRESSOR 



HISTONE NOT TURNING OVER 

 GENOME OF DIFFERENTIATED TISSUE 



a+ CID + CZD+ ■ 



DEGRADATION PRODUCTS 



Fig. 19. 



144 



