lect 14: genes and the genome II Flashcards
A ______ bond holds the nucleotide subunits in a single DNA strand, while a ________ bond holds the two DNA strands together?
phosphodiester; hydrogen
what is the difference between chromosome, chromatid and chromatin?
what is the graph of chromosome packing?
diff conformations of chromatin (all have DNA and histones)
what are the learning objectives of this lecture?
higher levels of chromosome structure
-nucleosomes: histone structure and histone code
-30nm chromatin fiber: cohesin
types of chromatin
-euchromatin
-heterochromatin
-effect of chromosomes structure of DNA function
what is the chromatin of higher levels of DNA structure?
-mitotic chromosome length=1 um
-length of contained DNA= 1 cm
-10,000:1 packing ratio
-incompletely understood process
why is DNA so small?
DNA double helix diameter is 2nm
-total length of human DNA lined up end-to-end > 7 ft but there is alot of it
average diameter of human cell nucleus is 6um, so how does the cell pack all this DNA into such a small place in an organized way?
-mitotic chromosome length=1um
-length of contained DNA=1 cm
-10,000:1 packing ratio (gets ten thousand times smaller)
-incompletely understood process
what is the first level of structure?
nucleosome: basic structural unit of eukaryotic chromosome
-DNA+ core complex (histone octamer)
-146 base pairs supercoiled DNA which wrap around core twice
histone proteins
-interact strongly with DNA (reversible)
-made of “basic” amino acids (i.e. positively charged like arginine and lysine) (helps hold to negative DNA strand)
-high level of conservation across organisms
what is the histone octamer and H1?
histone octamer: 4 histone heterodimers
-2 H3/H4 dimers
-2 H2A/H2B dimers
histone H1 (linker histone)
-compact chromatin globally
-stabilizes higher-order chromatin structures
-can be modified
what is histone structure?
- globular region (AKA histone fold)
-3 alpha-helices - histone tail
-N-terminus
-projects beyond DNA helix
-subject to modification
minor groove of DNA faces histone core
what is the figure of how histone looks like in 3D?
what is the other higher level structure of chromatin?
30-nm chromatin fiber
-chromatin fiber gathered into series of large, supercoiled loops (domains)
-DNA loops tethered at base to proteins (may be part of a poorly defined nuclear scaffold)
loops maintained by cohesin
-also holds replicated DNA molecules together during mitosis
what are the types of chromatin and the effect of chromosome structure on DNA function?
euchromatin: loosely packed
-due to availability: transcription factors need to access and reach (so we can have some gene expression)
heterochromatin: tightly packed
-constitutive
-facultative
what is constitutive and facultative heterochromatin?
constitutive
-always condensed, “silent” DNA
-centromeres, telomeres, distal arm of Y chromosome (dont need transcription factors to bind to it because they don’t code for anything)
-highly repeated sequences
-few genes in this region
faculatative
-inactivated during certain portions of organism’s life, or in certain cell types
-X-chromosome; Barr Body
what is the example of facultative heterochromatin?
the inactive X chromosome: calico cats
-only one X chromosome is transcriptionally active in female cells
-other X chromosome condensed as a heterochromatic clump (Barr body)
-X inactivation process is random
what is the histone code and formation of heterochromatin? (what makes chromatin pack loosely or tightly)
histone code hypothesis
-activity of chromatin region depends on degree of chemical modification of histone tails
histone tail modifications can:
1. serve as docking sites to recruit non-histone proteins
2. alter the way histones of neighboring nucleosomes interact
3 main chemical modifications of histone proteins:
-phosphorylation
-acetylation
-methylation
what is the most common site for histone protein modification?
-N-termini of H3 and H4 is common site of amino acid modification
-proteins may bind selectively to modified H3 or H4 residues
-heterochromatin has many methylated H3 histones- stabilization of the compact nature of the chromatin
what is the correlation between transcriptional activity and histone acetylation?
removal of acetyl groups from H3 and H4 histones
-an initial step in conversion of euchromatin to heterochromatin
-inactive, heterochromatic X chromosome=deacetylated histones (red)
-active, euchromatic X chromosome=normal level of acetylation (green)
what is epigenetics (there’s more to inheritance than DNA)?
epigenetics: inheritance that is not encoded in DNA
-e.g. X-chromosome inactivation
-inactivation is transmitted from parent cell to daughter cell throughout individual’s lifetime
epigenetic state may be reversed;
-e.g. X chromosomes reactivated prior to gamete formation
twin studies
-genetically identical
-differences in disease susceptibility and longevity
-due to epigenetic changes in twins as they age? (there must be environmental factors that alter inheritance)
which histone protein does not form the octameric histone core?
H1
which of the following is not a chemical group commonly found on core histone N-terminal tails for chromatin regulation?
a)methyl
b)sulfylhydryl
c)phosphoryl
d)acetyl
sulfhydryl
what are the relationships of genes, proteins and RNAs?
overview of the flow of information through the cell
transcription
-process by which RNA is formed from a DNA template
translation
-process by which proteins are synthesized in the cytoplasm from mRNA template
messenger RNA (mRNA)
-intermediated molecule between a gene and a polypeptide
