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Nucleosomes and Chromatin Structure Lodish Chapter 10.4 Organizing cellular DNA into chromosomes Most bacterial chromosomes are circular with one replication origin Eukaryotic chromosomes each contain one linear DNA molecule and multiple origins of replication

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organizing cellular dna into chromosomes

Nucleosomes and Chromatin Structure

Lodish Chapter 10.4

Organizing cellular DNA into chromosomes
  • Most bacterial chromosomes are circular with one replication origin
  • Eukaryotic chromosomes each contain one linear DNA molecule and multiple origins of replication
  • Bacterial DNA is associated with polyamines
  • Eukaryotic DNA associates with histones to form chromatin
slide13
Epigenetics: changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence

Histone modifications

 acetylation (histone acetyl-transferases – HATs); associated with active chromatin

 de-acetylation (histone deacetylases – HDACs); associated with inactive chromatin (new generation of anti-cancer drugs: HDAC inhibitors)

 methylation (can be associated with active or inactive, depending on site of modification)

 phosphorylation (metaphase chromosomes)

DNA methylation

 DNA methyltransferases (Dnmt1, 3a, 3b) associated with inactive chromatin)

slide16

DNA can be condensed to heterochromatin

Euchromatin Heterochromatin

slide17

Giemsa

stained

bone

marrow

stem cell

slide21

Lack of telomeres facilitates chromosome fusion

Visualizing telomeres by fluorescent in situ

hybridization (FISH)

each chromosome has a characteristic banding pattern
Each chromosome has a characteristic banding pattern

Organization of metaphase chromosome:

  • Chromosome bands:
      • Common technique is G-banding (Giemsa). Chromosomes prepared from metaphase cells, stained with Giemsa. Dark bands are called G bands, pale bands are G negative. Dark bands are generally late replicating, contain more condensed chromatin and are less transcriptionally active while light bands are the opposite.
slide23

Organization of metaphase chromosome

Common technique is G-banding (Giemsa). Dark bands are

called G bands (heterochromatin), pale bands are G negative (euchromatin).

slide24

Nomenclature: p (pepit) arm = short arm; q=long arm.

  • Band numbering proceeds outwards from the
  • centromere e.g., bands p11 (one-one NOT eleven)
  • or p23(p two-three NOT twenty three)
slide28

Chromosome translocations can also play

a role in evolution

Tree shrew

SNL crew

genome sizes of different model organisms
Genome sizes of different model organisms

Yeast 12M bp/ 16 chromosomes

Flies 180 Mbp/ 3 autosomes, X and Y

Zebrafish 1,700 Mbp/ 25 chromosomes

Mice 2,600 Mbp/ 19 autosomes, X and Y

Humans 3,900 Mbp/ 22 autosomes, X and Y

slide30

What you need to know:

DNA is wrapped around histones

Loops in 300 nm fiber bring regions that are largely spaced apart

into close proximity (will be important for transcriptional regulation)

Dimension of beads on a string = 11 nm; chromtin fiber = 30 nm)

Histones: 5 histone proteins (H1, H2a, H2b, H3, H4) H1 is linker histone

tightens DNA around histone core

Histone octamer composed of 2a, 2b, 3, 4 TWO copies each

Histone octamer plus DNA is a nucleosome. Histones are important for

compaction of DNA but do also serve regulatory functions by means of

modification

Which histone modifications are associated with active/inactive chromatin

(acetylation, methylation, phosphorylation. Metaphase chromosomes are

usually phosphorylated-facilitates condensation)

Euchromatin (active), Heterochromatin (more condensed, inactive)

Chromosome nomenclature (p and q arms)

Telomere function- protect chromosome ends from fusing

Genome sizes of different organisms