Nov 27 Chapter 11 (continued)

B. Gene regulation in eukaryotes (continued)

               

ii) Chromatin structure (Fig 11.6, p215)

- Histones attach to DNA to make the ‘beads on a string’ structure.

- Each ‘bead’ is also called nucleosome.

- Nucleosome consists of DNA wound around eight histone protein molecules.

- Chromatin can be further packed to make the tight helical fiber or the supercoil structure.

- Tight packing of chromatin turns off gene expression because it prevents RNA polymerase to access DNA.

            Example 1: Condensed chromatins during metaphase are inactive.

            Example 2: (Fig 11.7, p217)

·         In somatic cells of female mammals, one of the two X chromosomes is condensed all the time (X- chromosome inactivation).

·         Patchy fur color of a cat is due to the X chromosome inactivation.

 

- Chromatin must be loosened first to turn on gene expression.

- Histones detach from DNA to allow RNA polymerase to access DNA.  

 

iii) Transcriptional regulation (Fig 11.8, p217)

Major controlling point of gene expression.

Enhancers / silencers: regulatory DNA sequences (analogous to operators in prokaryotic gene). 

- One gene is controlled by multiple enhancer / silencer elements

Transcription factors: regulatory proteins for transcription.

 

- Activator proteins bind to the enhancer sequences.

- Other transcription factors interact with activator proteins to make a protein complex.

- The transcription factors also interact with RNA polymerase to assist the binding of RNA polymerase to the promoter sequence.    

- Repressor proteins bind to the silencer sequences, which inhibits the binding of RNA polymerase to the promoter sequence.

Alternative splicing

           

 

iv) Posttranscriptional regulation

a. RNA processing

- RNA processing is critical for expression of eukaryotic genes.

- In some cases, different polypeptides can be produced from a single gene via alternative splicing. 

 

b. mRNA breakdown

- The rates of mRNA breakdown vary among mRNA molecules. Some mRNAs stay in the cytoplasm much longer than others.                                                Example of long lived mRNA: hemoglobin mRNAs in red blood cells

- The breakdown of mRNA is catalyzed by RNA degrading enzymes (RNases). 

 

c. Translation

- Regulatory proteins may control the initiation process of translation.

 

d. Protein activation

- Newly translated polypeptides are not functional until they are shaped into proper forms.

- The process of protein activation may involve: proper protein folding, cleavage (see example of insulin below), modification (such as adding sugar chains), assembly to a larger protein complex, etc.

e. Protein breakdown

- The rates of protein breakdown can vary among proteins. 

- Breakdown of proteins is important for regulating protein concentrations in the cells.

            Example: The concentration of cell cycle proteins, such as cyclins, is tightly regulated.

- Damaged proteins are removed and replaced by new ones.

 

v) Mechanisms of Signal Perception (Fig 11.13, p221)

(1) Signal molecules, such as hormones and growth factors, are produced by signaling cells.

(2) The signal molecule binds to the specific receptor proteins that are embedded in the target cell’s plasma membrane.

(3) The binding activates the signal transduction pathway.  The signal transduction pathway consists of a series of relay proteins.  Each relay protein activates another.

(4) At the end of the signal transduction pathway, the last relay protein activates a transcription factor.

(5) The transcription factor turn ON the expression of target genes.