Question

You are working with a population of multi-potent stem cells that you grow in a tissue culture dish. They have the capacity to differentiate into any one of three possible differentiated cell types (alpha, beta, delta) if they are first exposed to a signaling factor (Bmp4) for 24 hours and then cultured without this factor for another 24 hours. The specific choice the cells make after treatment (alpha or beta or delta) is more or less random among the cells in the dish but all cells do make one of the three choices if they treated with the factor and then cultured without it. Cells do not choose any of the three identities if they are just left untreated entirely.

Each of cell type is defined by the expression of a unique gene:

alpha cell express gene A, but not genes B or D,

beta cells express gene B, but not gene A or D, and

delta cells express gene D, but not genes A or B.

Describe or depict a gene regulatory network (circuit) that could function in the cells to allow them to uniquely express gene A or B or D after the treatment (24hrs with Bmp4, followed by 24 hrs without it).

Answer 1

ANSWER :-

1. This process is very much related to gene silencing. In this case, it is stated that every possible phenotypic outcome is being mediated in the presence of a particular gene such as gene A in case of the alpha cells.
2. This indicates that on one hand, a particular gene has been expressed whereas on the other hand the remaining two genes not associated with the output are repressed mainly by means of inactivation.
3. There are regulatory sequences or elements which are associated with every gene to which a repressor protein moiety can bind or sequence alteration can occur such that the gene expression is being affected or more specifically inhibited.
4. One such way in which the regulation mentioned above can be mediated is by means of DNA methylation taking into consideration all the genes follow a same pattern for expression of their related phenotype. DNA methylation is a process wherein there is addition of a Methyl (-CH3) group to a cytosine nucleotide in the sequence. The main point to be mentioned over here is that the regulatory elements are characterized with presence of CpG islands or sequence which is rich in the two nucleotides namely cytosine and guanine thereby enhancing an effective control on the process of DNA Methylation. Addition of a methyl group silents the process of gene transcription.
5. In case of synthesis of gene A, a signal might be mediated which will activate the DNA methylation mechanism of the remaining two genes thereby resulting in sole expression of the gene responsible for a particular phenotype.

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