116
HERMAN DENIS
possible a new approach to the problem of differentiation. The essential
question can be stated as follows: "In what way is the genetic information contained in the single set of chromosomes (i.e., an ordered sequence
of nucleotides) of the fertilized egg expressed in the form of the many different cell types making up the adult organism?"
The organs and the tissues of the adult organism differ essentially
from one another by the proteins they contain. Information concerning
the structure of each individual protein is contained in the deoxyribonucleic acid (DNA) of each cell. In any one tissue, only a given fraction
of the information enclosed in the DNA is transcribed and translated
into protein; whereas, in another tissue, a different portion of the genome
is expressed (MacCarthy and Hoyer, 1964). A mechanism must, therefore, exist in each cell whereby a finite part of the genome is selected for
translation into proteins, thus distinguishing the cell type with its specific
morphological and physiological properties. Such a mechanism must play
an essential role in embryonic development. One can, a priori, imagine
that the selection of the genetic information leading to cellular differentiation occurs at three distinct levels of the transmission chain: DNAmessenger ribonucleic acid (mRNA)-protein.
1. At the level of the DNA itself. In a differentiated cell, a definite
part of the genome would be made inaccessible for transcription by a
chemical modification of the DNA itself. The change that is most frequently alluded to is an alkylation and particularly a methylation
(Srinivasan and Borek, 1964; Scarano and Augusti-Tocco, 1967). The
existence of enzymes able to methylate DNA has been proved (Gold
et al., 1963; Gold and Hurwitz, 1964a,b); on the other hand, a progressive methylation of DNA seems to take place during the development of
the sea urchin (Scarano et al., 1965).
2. At the level of the transcription
mechanism.
In all differentiated
cells DNA would be in the same chemical and physical state. MacCarthy
and Hoyer (1964) and Denis (1967) compared the DNA's extracted
from several tissues of the mouse and of Xenopus and could not detect
any difference in the nucleotide sequences that make up the various
DNA's tested. As the sensitivity of the method used was limited, the experiments did not exclude the existence of subtle differences between the
various preparations of DNA.
If DNA is really in exactly the same state in all cells of the organism,
the genetic information could be selected in the following way. Only the
region of the genome to be expressed would be accessible to the transcribing enzymes; the other regions would be covered or "repressed." The
HERMAN DENIS
possible a new approach to the problem of differentiation. The essential
question can be stated as follows: "In what way is the genetic information contained in the single set of chromosomes (i.e., an ordered sequence
of nucleotides) of the fertilized egg expressed in the form of the many different cell types making up the adult organism?"
The organs and the tissues of the adult organism differ essentially
from one another by the proteins they contain. Information concerning
the structure of each individual protein is contained in the deoxyribonucleic acid (DNA) of each cell. In any one tissue, only a given fraction
of the information enclosed in the DNA is transcribed and translated
into protein; whereas, in another tissue, a different portion of the genome
is expressed (MacCarthy and Hoyer, 1964). A mechanism must, therefore, exist in each cell whereby a finite part of the genome is selected for
translation into proteins, thus distinguishing the cell type with its specific
morphological and physiological properties. Such a mechanism must play
an essential role in embryonic development. One can, a priori, imagine
that the selection of the genetic information leading to cellular differentiation occurs at three distinct levels of the transmission chain: DNAmessenger ribonucleic acid (mRNA)-protein.
1. At the level of the DNA itself. In a differentiated cell, a definite
part of the genome would be made inaccessible for transcription by a
chemical modification of the DNA itself. The change that is most frequently alluded to is an alkylation and particularly a methylation
(Srinivasan and Borek, 1964; Scarano and Augusti-Tocco, 1967). The
existence of enzymes able to methylate DNA has been proved (Gold
et al., 1963; Gold and Hurwitz, 1964a,b); on the other hand, a progressive methylation of DNA seems to take place during the development of
the sea urchin (Scarano et al., 1965).
2. At the level of the transcription
mechanism.
In all differentiated
cells DNA would be in the same chemical and physical state. MacCarthy
and Hoyer (1964) and Denis (1967) compared the DNA's extracted
from several tissues of the mouse and of Xenopus and could not detect
any difference in the nucleotide sequences that make up the various
DNA's tested. As the sensitivity of the method used was limited, the experiments did not exclude the existence of subtle differences between the
various preparations of DNA.
If DNA is really in exactly the same state in all cells of the organism,
the genetic information could be selected in the following way. Only the
region of the genome to be expressed would be accessible to the transcribing enzymes; the other regions would be covered or "repressed." The