Lecture 1-2: DNA, Chromosomes and Genomes Flashcards
Examples of Epigenetics (3)
DNA methylation Chromatin structure Histone modification
ATP-dependent chromatin remodeling protein is located where
On reader writer complex. Uses ATP to either condense or decondense long stretches of chromatin
Chromatin consists of
Nuclear DNA + Protein
Purifying Selection
Elimination of mutations that interfere with important genetic functions
Phosphorylation of serine (covalent modification)
Gene activates
SNPs
Single nucleotide polymorphism Points in genome where one group has one nucleotide and another group has another
Acetylation of lysines (covalent modification)
Loosens chromatin structure (added by histone acetyl transferases, removed by histone deacetylase complexes)
Duplication and divergence
Both copies of gene maintain functional while diverging in sequence and pattern of expression
Pseudogenes
A duplicated gene that has become irreversibly inactivated by mutations
HS4 region
Contains cluster of histone acetylase binding sites, protects beta-globulin locus from silencing
Nucleosome consists of
8 histone proteins (histone octamer) DS-DNA that is 147 nucleotide pairs long
Condensation of chromosomes function
Disentanglement of sister chromatids Protection of fragile DNA molecule as separation occurs
Epigenetics
A form of inheritance that is superimposed on the genetic inheritance based on DNA
Interactions between DNA and histone
H-bonds Hydrophobic interactions Salt linkages (1/5 of histone residues are lysine or argenine +)
Barrier sequence function
Halt the spread of chromatin modifications
Chromatin remodeling complex
Allow further loosening of DNA/histone contact Changes structure of DNA temporarily, making DNA less tightly bound
Zone of inactivation
Area around heterochromatin, can spread different distances in different cells
DNA condensation is a ____ situation
Dynamic
Nucleosome
Most basic unit of chromosome packing
Final level in chromosome packing is during
Mitosis, very condensed
of hydrogen bonds formed between histone core and DNA in each nucleosome
142 H-bonds
Chromosome requirements (3)
DNA replication origin Centromeres Telomeres
Nucleotides are made of
5-carbon sugar and nitrogenous base covalently linked via glycosidic bond
Chromosomes during interphase:
Chromosomes are replicated; they are decondensed and difficult to distinguish
Position effect variegation
Breakage events that bring heterochromatin near active genes tends to silence them
Position effect
Activity of a gene depends on position on the chromosome
Lysine methylation (covalent modification)
Silences genes (added by methyl transferases, removed by demethylases)
Histone code read by
Code reader complex Involves joint recognition of histone tail and covalent modification
Nucleosome packing
Forms dense fibrous structure with diameter of 30nm
Heterochromatin is very concentrated near
Telomeres and centromeres
Histone code determines
Determines how/when DNA is packaged in nucleosome
Histone H1
Linker histone Contacts both DNA and protein Changes path of DNA as it exits nucleosome
Heterochromatin location in nucleus
Usually associates with nuclear lamina
Types of barrier sequences
Physical barriers Enzymatic barriers
8 Histone proteins include
2 molecules each of H2A, H2B, H3, H4
How can various possible chromatin structures arise
Specialized variant histones
Centromeric sequences
Consist of short repetitive DNA sequences called alpha satellite DNA Defined by assembly of proteins (i.e., H3 histone), not DNA sequence Centromeres can form spontaneously w/o alpha satellite DNA sequence
Interphase chromosome structure
Lampbrush- series of large chromatin loops emanating from a linear chromosome axis
Translocation of chromosome 9&22 form
Philadelphia chromosome on chromosome 22. Commonly found in CML
Homologues
Genes that are similar in both sequence and function due to common ancestry
Building blocks of DNA
Nucleic acids
How are different activities localized in the nucleus
Different neighborhoods have effects on gene expression.
Nucleotides are joined together via
Phosphodiester linkage between 5’ and 3’ carbon atoms
CNVs
Copy number variants Presence of many duplications and deletions of large blocks of DNA
Chromosomes during mitosis
Chromosomes are highly condensed and separated into two daughter nuclei
Histone tails
Help to condense chromatin Largely unstructured, highly flexible Can form interactions with adjacent nucleosomes
Heterochromatin
Very condensed chromatin, stains darkly throughout the cell cycle, even interphase
Condensins
Use ATP hydrolysis to coil DNA molecules into chromatids
Major histones are synthesized and assembled when
Synthesized during S-phase Assembled into nucleosomes on daughter DNA helices just behind replication fork
Code reader-writer complex
Reads modifications and spreads them to nearby nucleosomes
Percentage of DNA sequence in exons
1.5%
Nucleosomes repeat every _#_ nucleotides
~200 nucleotides between
Varient histones synthesized and inserted when
Synthesized during interphase Inserted into already-fromed chromatin, REQUIRES histone exchange process catalyzed by chromatin remodeling complex
How do genomic changes occur
Mistakes in DNA replication and repair Movement of transposable elements
Reasons for sequence conservation
Not having enough time for mutations to occur since lineages separted Purifying selection