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How Genes Are Controlled

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Title: How Genes Are Controlled


1
Chapter 11
  • How Genes Are Controlled

2
How and Why Genes Are Regulated
  • 4 separate cells types all very different in
    shape and function but all share the same DNA
  • They are different because of the genes that are
    turned on or off called cellular differentiation

3
Patterns of Gene Expression
  • If gene is turned on if it is made into mRNA and
    then a protein that will determine the cells
    phenotype
  • Information goes from gene to protein genotype
    to phenotype
  • process is call gene expression
  • different genes on in different cells

4
Gene Regulation in Bacteria
  • Bacteria do not differentiate but make proteins
    based on nutrients available in their environment
  • We have E coli in our digestive tracts if we
    eat an ice cream cone the bacteria needs to make
    the proteins necessary to digest lactose
  • takes 3 enzymes to do this
  • when lactose is gone, the enzymes are removed as
    the bacteria do not want to waste energy making
    proteins that they dont need

5
lac Operon
  • 3 genes are next to each other in the DNA and are
    turned on or off together
  • will make all or none
  • Called an operon mechanism of how genes are
    regulated in bacteria
  • Genes are all under the direction of one promoter
    site where transcription enzyme (RNA
    polymerase) attaches and starts transcription
  • Between the promoter and gene is another
    regulator sequence called the operator which
    helps to turn the genes on or off whether there
    is a protein bound or not

6
Operator Control
  • When there is NO lactose available as food source
    a protein called the repressor is bound on the
    operator and the RNA polymerase cant bind and
    initiate transcription
  • When lactose IS present, then the repressor is
    inactivated and the RNA polymerase can bind and
    make mRNA and subsequently protein
  • Operons are also used to make the proteins
    necessary for making amino acids if they are not
    in the food source

7
Gene Regulation in Eukaryotic Cells
  • We do not have operons like bacteria, the system
    is more elaborate
  • Number of points where process from DNA to
    protein that can be regulated
  • on or off speed up or slow down
  • similar to regulating water in the pipes from the
    city to your house

8
Regulation Spots
9
1. DNA Packaging
  • Chromosomes may be in more or less condensed
    state more tightly packed or loosely packed
  • packing prevents gene expression cant get the
    RNA polymerase and other machinery in, then no
    transcription
  • See packaging in X chromosome only 1 X is
    active in each somatic cell
  • the 2nd X is tightly packed and completely
    inactivated done during embryonic development
  • the X that is active is random and passed on to
    all cells that parent cell
  • see in tortoiseshell cat which X inactivated
    will dictate the coat color

10
2. Initiation of Transcription
  • Most important level of control
  • Use regulatory proteins all genes have own
    promoter and control sequences
  • Use transcription factors to bind enhancers and
    promoter as complex recruits RNA polymerase
  • May also have silencers that repress gene
    expression or an activator to turn on gene
  • not many repressors
  • default is to be off unless it is a
    housekeeping gene that must always be on

11
3. RNA Processing and Breakdown
  • RNA transcription is done in the nucleus and RNA
    must be modified before going out to cytoplasm
  • Cap at 5 end and tail at 3 end to protect the
    mRNA
  • must remove the non-coding sequence called
    introns, link exons together to make mRNA
  • can mix and match exons to make related proteins
    called alternative RNA splicing
  • Length of time the mRNA stays around will
    determine the number of times it is used for
    making protein

12
4. Regulate Translation
  • Once the mRNA leaves the cytoplasm, there is a
    decision to be made make or destroy message
  • Other proteins help in making this decision
  • cant make the globin portion of hemoglobin if
    there is not an available supply of heme
  • will also need to make sure there is adequate
    energy and amino acids available for protein
    synthesis

13
5. Protein Alterations and Breakdown
  • Last chance for control occurs after protein is
    made
  • Post-translational control involves modifying
    the protein to make it a functional molecule
  • insulin needs a cleavage event to make it active
  • Also have selective breakdown some proteins are
    needed only for a short time so need to breakdown
    and recycle amino acids

14
Cloning
  • Can be used to make new organism or to make
    replacement organs and tissues
  • The making of tissues is thought to be linked to
    stem cells cells that have the potential to
    become any cell providing they are given all the
    right materials and information stem cells
  • 3 types of cells
  • embryonic stem cells
  • adult stem cells
  • umbilical cord blood stem cells

15
Embryonic Stem Cells
  • Made from early embryonic state called blastocyst
    hollow ball of cells that form a few days after
    fertilization but before implantation
  • Cells can give rise to all specialized cells in
    organism
  • use certain growth factors to change gene
    expression
  • has the most potential

16
Adult Stem Cells
  • Present in adult tissue and generate replacements
    for non-dividing differentiated cells
  • These cells have made some decisions and
    therefore not as plastic as embryonic stem cells
    cant make all cells
  • Harder to grow in culture
  • May be used in tissue and organ transplant

17
Umbilical Cord Blood
  • Stem cells taken from umbilical cord and placenta
    cells are partially differentiated but not as
    much as adult stem cells
  • People are banking them for their children in
    case they need something down the line
  • not sure if this will work and if it is worth the
    expense as we dont have evidence that this will
    live up to the promise

18
Genetic Bases of Cancer
  • Caused by escape from normal cell division
    changes in some of the cells genes or to the way
    certain genes are expressed
  • Earliest evidence that genes cause cancer was a
    virus that caused cancer in chickens
  • several viruses can cause cancer as they have
    genes that induce tumor growth
  • called oncogenes

19
Oncogenes
  • Altered version of a normal gene see these in
    genomes other than just viruses including humans
  • Normal gene that has the potential to become an
    oncogene is a proto-oncogene
  • many encode for growth factors that stimulate
    cell division or other proteins that affect the
    cell cycle
  • when functioning normally or in the right amounts
    cell division is normal

20
Becoming an Oncogene
  • 3 types of things happen to the gene that alters
    its function mutation in the cells DNA
  • mutation within the gene
  • over production of the gene product
  • movement of the gene to a different area that is
    under a different control mechanism

21
Tumor Suppressor Genes
  • Genes that prevent the formation are called tumor
    suppressor genes
  • Changes in these genes can lead to cancer
    development usually a mutation that makes an
    inactive form of the protein

22
  • Most proto-oncogenes and tumor suppressor genes
    code for proteins that function in signal
    transduction pathways

23
Cancer Formation
  • More than 1 change required to produce cancer
  • Uncontrolled cell growth parallels changes in the
    DNA

24
Inherited Cancer
  • Cancer is a genetic disease but usually only in 1
    organ system changes cannot be passed on unless
    the change was in the egg or sperm
  • may have mutation in gamete that predispose them
    to cancer but still need additional malfunctions
    to actually get
  • Some breast and ovarian cancers have a genetic
    link BCRA 1 and BRCA2 (tumor suppressor gene)
  • these genes increases the risk for cancer but
    still need an additional hit
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