Eukaryotic Genomes Part II

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Translational and Posttranslational Control.

-          Translation in eukaryotes involve more initiation factors.

-          Most translational control mechanisms block the initiation phase of proteins synthesis.

-          Translational repression proteins that bind to specific sequences or structures at the 5’ ends of particular messages.  This prevents the attachment of ribosomes.

-          Translation may also be blocked by proteins that inactivate initiation factors.

-          Eukaryotic polypeptides must be processed to yield the active final products.

-          Many polypeptides must be modified by the addition of chemical groups such as chains of sugars to be active.

-          In other cases, a signal mechanism must target these proteins.

-          Regulation may occur at any of these steps in modification or transport.

-          The final step is the cell’s selective degradation of particular proteins.

-          If the wrong proteins are selected, diseases like cystic fibrosis may occur.

The Arrangement of Coordinately Controlled Genes.

-          Different genes of related function need to be turned on or off at the same time.

-          Normally, these genes are clustered in an operon.  All genes of an operon are transcribe sequentially.  These genes have not been found in the eukaryotic cell.

-          Genes coding for enzymes in metabolic pathways are often scattered over different chromosomes.  Even when they are found near each other, they still have their own promoter and are transcribed individually.

-          Coordinate gene expression involves the presence of a specific regulatory element r enhancer associated with every gene of the group.

-          This sequence is recognized by a single transcription factor that acts as the operator.

Gene Expression and Differentiation

-          In multicellular organisms, there is a high degree of cellular differentiation resulting in the formation of different tissue.

-          This differentiation yields major changes in the structure and function of the cell. And can only occur as a result of the presence or absence of tissue-specific proteins.

-          Chemical signals affect only certain cells or groups of cells.

-          The function of these signals is to activate transcription factors which result in the expression of regulatory proteins.

Chemical Signals That Help Control

-          In eukaryotes, many small organic molecules influence transcription by combining with regulatory proteins.

-          These include steroid hormones.

Chromosomes Puffs

-          A puff forms when DNA loops out from the chromosome axis and perhaps is making the DNA region more accessible to transcription.

-          The locations of chromosomes puffs change with development.

-          These were first studied in insect larvae.

-          The shifting puffs are visual indicators of the development.

The Action of Steroid Hormones in Vertebrates

-          Steroids are soluble lipids.

-          When a cell is exposed to a steroid, the hormone diffuses across the plasma membrane into the cytoplasm and then enters the nucleus where it encounters a soluble receptor protein and then binds to the receptor protein.

-          In the absence of the steroid, the receptor protein is usually associated with an inhibitory protein that prevents the receptor from binding to DNA.

-          Binding of the steroid to the receptor causes the release of the inhibitory protein and the activated receptor protein can now attach to specific sites on the DNA.

-          These sites are within enhancers or regulatory regions.

-          Binding of the receptor protein to the enhancer activates transcription.

-          Other hormones can affect transcription.

-          These hormones are not lipid soluble and cannot cross cell membranes and must operate through a receptor protein on the outside of the cell.

-          The binding initiates a signal transduction pathway that leads to the activation of specific transcription factors. 

Chemical Modification or Relocation

-          Sometimes the number of copies of a gene or gene family may increase in some tissues during different stages of development..

-          This is caused by selective replication of certain genes also known as gene amplification and is a means of increasing expression of genes.

-          This has also been observed in cancer cells exposed to high concentrations of chemotherapy.

-          The drugs may kill many cells but invariably some are resistant.

-          Increasing concentrations of such drugs lead to increasing resistance in the cell population.

Rearrangements in the Genome

-          All organisms seem to have transposons, stretches of DNA that are particularly prone to moving from one location to another within the genome.

-          If the transposon jumps into the middle of a coding sequence, it prevents the normal functioning of the interrupted gene.

-          If the transposon inserts into the middle of a regulatory gene, it may increase or decrease the production of one or more proteins.

-          The transposon itself carries a gene that is activated when inserted downstream from an active promoter.

-          In vertebrates, at least one set of genes undergoes permanent rearrangement. 

-          These are immunoglobulins or genes that code for antibodies.

-          The proteins specifically recognize and help combat viruses, bacteria, and other invaders.

-          They are made by cells of the immune system called B lymphocytes (a type of white blood cell).

-          They are highly specialized.

-          An unspecialized cell can differentiate into a B lymphocyte when segments of antibody genes are pieced together randomly from several DNA regions that are physically separated in the genome.

DNA Methylation

-          This is when the nitrogenous bases of DNA are sometimes modified by a process called methylation.

-          This is the addition of methyl groups to bases of DNA after synthesis.

-          The DNA of most plants and animals has this and the base is usually cytosine.

-          This makes them inactive.

Cancer

-          Certain genes normally regulate cell growth and division and mutations in these cells can alter their expression and lead to cancer.

-          Most of these mutations occur as a result of an environmental influence.

-          Harold Varmus and Michael Bishop found the oncogenes which are cancer causing genes.

-          They noticed that oncogenes in certain retroviruses caused uncontrolled growth of infected cells in culture.

-          The counterparts of these genes are called proto-oncogenes. 

-          These are normal genes that code for protein products that normally regulate cell growth, division, and adhesion.

-          The products of the proto-oncogenes become more active as a result in changes leading to increased gene expression. 

-          These mutations in the proto-oncogene may be caused by gene amplification, chromosome translocation, transposition, and point mutation.

-          Malignant cells are frequently found to contain translocated fragments of chromosomes.

-          The oncogene found in the new joint region may now be adjacent to active promoters that increase transcription.

-          Conversely, a promoter may be moved near the oncogene with the same effects.

-          Changes in genes that prohibit cel division may also be involved.  These are called tumor suppressor genes because the proteins they code for normally help prevent uncontrolled cell division.

-          Any mutation that decreases the normal activity of tumor-suppressor proteins may contribute to the onset of cancer and stimulate growth.

-          Normally, more than one somatic mutation is generally need to produce all the changes characteristic to a cancer cell.