Gene Expression

Cell Differentiation Cell types are different because genes are expressed differently in them. Causes:  Changes in chromatin structure  Initiation of transcription  RNA processing  mRNA degradation  Translation  Protein processing and degradation

Operons  Unit of genetic function consisting of related clusters of genes with related functions  A “switch” that controls enzyme production  Coded for by one transcription unit

Repressible Operons (The trp Operon)  Repressible Operon: always operates unless a repressor turns it off.  promoter: RNA polymerase binding site; begins transcription  operator: controls access of RNA polymerase to genes  transcription stops here when repressor is in place  repressor: protein that binds to operator and prevents attachment of RNA polymerase  Sometimes, a corepressor must be in place for the repressor to be active  Tryptophan (a.a.) synthesis  Transcription is repressed when tryptophan binds to the repressor, which connects to the operator

Inducible Operons (The lac operon)  Inducible Operon: Always off unless an inducer is present  Inducer attaches to the repressor and causes it to move so that transcription can occur  Lactose metabolism (lac operon)  lactose not present: repressor active, operon off; no transcription for lactose enzymes  lactose present: repressor inactive, operon on  inducer molecule inactivates protein repressor (allolactose)

Chromatin  Complex of DNA and proteins  DNA Packing  histone protein (+ charged amino acids ~ phosphates of DNA are - charged)  Nucleosome  ”beads on a string”  basic unit of DNA packing  Heterochromatin  highly condensed interphase DNA (can not be transcribed)  Euchromatin  “true chromatin”  less compacted interphase DNA (can be transcribed)

Histone Modification  Genes within highly packed heterochromatin are usually not expressed  Chemical modifications to histones and DNA of chromatin influence both chromatin structure and gene expression  Acetylation prevents histones from packing tightly, which allows genes to be expressed.  Methylation causes histones to pack tightly so that genes are not expressed.

Epigenetic Inheritance  Expression of traits is not necessarily related to the nucleotide sequence  Some individuals may express traits from their genes where others will not based on histone modifications  One twin may express a trait or get a disease that the other does not, despite same genes  Schizophrenia  Some cancers  Etc.

Regulation of Transcription  Control Elements- noncoding DNA that regulate binding proteins  Enhancers- segments that influence how a gene is expressed  Often placed far from the actual gene

RNA and Protein Processing  Alternative RNA splicing  Different mRNA molecules formed from the same primary transcript  mRNA degradation  Protein processing  Protein degradation  proteasomes

Cell Differentiation  How cells become specialized in structure and function.  Determinants exist in the egg cell  Influence the expression of characteristics in different regions of cells  Once cells divide by mitosis, specific regions of the embryo will express genes differently

(b) Induction by nearby cells (a) Cytoplasmic determinants in the egg Two different cytoplasmic determinants Unfertilized egg cell Sperm Fertilization Zygote Mitotic cell division Two-celled embryo Signal molecule (inducer) Signal transduction pathway Early embryo (32 cells) Nucleus NUCLEUS Signal receptor

Body Plan Setup Pattern Formation  cytoplasmic determinants  inductive signals  determine spatial organization of tissues

Biology of Cancer   Oncogene- cancer-causing genes   Proto-oncogene- normal cellular genes   How does a proto-oncogene become an oncogene?   movement of DNA; chromosome fragments that have rejoined incorrectly   amplification; increases the number of copies of proto-oncogenes   point mutation; protein product more active or more resistant to degradation   Tumor-suppressor genes   changes in genes that prevent uncontrolled cell growth (cancer growth stimulated by the absence of suppression)

ras and p53  ras   Produces Ras proteins   Hyperactive Ras protein causes cell cycle to continue (increased cell division)   Mutations involved in 30% of all cancers  p53   Tumor-suppressor gene   Activated by DNA damage   Turns on DNA repair or activates “suicide” genes   Mutations involved in 50% of all cancers