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70 Cards in this Set

  • Front
  • Back

chromatin

the nucleoprotein complex that DNA is condensed into

nucleosome

fundamental unit of chromatin structure

nucleosome consists of...

segment of 146 base pairs of DNA wrapped 1.6 times around a nucleosome core particle make up of 8 histone molecules

the 8 core histones

H2A, H2B, H3, H4

properties of core histones

positively charged


spontaneously dimerize


spontaneously self-assemble into ncp/s


highly conserved

core histones contain:

a helix-loop-helix-loop-helix domain


long N-terminal tails

the conservation of histone amino acid sequences is most likely due to what type of selection?

purifying selection

linker DNA

segments connect adjacent nucleosomes


length varies between taxa

histone H1

stabilizes the junction of the linker DNA with the nucleosome core particle

Nucleosome synthesis

nucleosomes are displaced and denatured into histone dimers ad tetramers by the replication fork


H3-H4 tetramers quickly reaffiliate with the daughter duplexes ~600 bp behind the fork


H2A-H2B dimers are the added

histone chaperones

ASF-1 and CAF-1


facilitate the nucleosome synthesis

intrinsic mechanisms

the positions are determined in part by the DNA sequence itself, which can favor or disfavor DNA-histone associations

Extrinsic mechanisms

the position of the first nucleosome is a region is controlled by other proteins and this affects the positions of the neighboring nucleosomes

intrinsic positioning

not accomplished by fixed DNA motifs, but rather by the general physical properities of the nucleotide sequence

nucleosome assembly is favored by...

favored by alternating AT and GC dinucleotides (every 5 base pairs)

Nucleosomes are excluded by...

excluded by Poly dAdT tracts

chromatin lowest level of organization

10-nm fiber, which has a "beads on a string" appearance


this achieves ~6-fold compaction of the DNA


the 10-nm fiber only exists transiently under normal cellular conditions

chromatin second level of organization

under normal conditions, the 10-nm fiber folds into a solenoidal structure that gives rise to the 30-nm fiber


each turn containes 8-10 nucleosomes


this provides a further 6-fold compaction of the DNA

Higher order chromosomes structures are based on...

chromatin loops anchored to a nonhistone protein scaffold


each chromatin loop contains 20,00-100,00 bp


loops attach to the chromosome scaffold at matrix attachment regions

matrix attachment regions

often associated with DNA repeats called ATC sequences

Chromatin loops

cell-dependent and affects gene expression


formed by scaffold proteins


are organized into rosettes and bundles, resulting in a further 250-fold compaction of the DNA

how many histone molecules make up the nucleosome core particle?

8

Approximately how many nucleosomes can fit into a 1 Mb segment of the human genome?

5000


each nucleosome has 146 bp of DNA wrapped around the nucleosome core particle as well as ~50 bp of linker DNA, for a total of ~200 bp. Dividing 1,000,000 by 200 shows that approximately 5,000 nucleosomes will fit into this segment

Protamines

basic proteins that Spermatid DNA is mainly packaged with


bind in the major groove of DNA and neutralize the phosphodiester backbone


__-DNA complexes coil into toroidal structures "donut-loop" of ~50 kb DNA


Sperm DNA is highly condensed and largely transcriptionally silent

Dinoflagellates

unique among eukaryotes in lacking nucleosomes


flagellated planktonic protists


their nuclei contain up to 30x as much DNA as human cells


DNA is packaged using a unique class of ___/Viral NucleoProteins also found in Phycodnaviridae viruses


the use of DVNP's appears to be derived, possibly resulting from horizontal transfer of a DVNP gene from a virus

Heterochromatin

highly condensed and is transcriptionally repressed (no expressed genes)


shows up as dark chromosome bands (G-bands)

Euchromatin

relatively open and contains most expressed genes


shows up as light chromosome bands

Constitutive heterochromatin

permanently condensed


transcriptionally repressed


mainly composed of satellite DNA (tandem repeats)


locations: centromeres, telomeres, transposons

Facultative heterochromatin

reversibly condensed


contains silent genes that can be activated


differs between cell types


Ex: Barr body formation results in the formation of ___

During which stage of the cell cycle are chromosomes least condensed?

interphase

chromosome condensation

maximal during metaphase


minimal during interphase

p arm

short arm

q arm

long arm

Metacentric chromosomes

arms are similar lengths

Submetacentric chromosomes

distinctly shorter p arms

acrocentric chromosomes

very short p arms composed of mainly repetitive satellite DNA

Telocentric chromosomes

have a terminal centromere (no p arm)

karyotype

shows the number and shape of an organisms chromosomes

human karyotype:

5 metacentric chromosomes


13 submetacentric chromosomes


6 acrocentric chromosomes

Chromosomes territories

the area that chromosomes occupy during interphase


vary from cell to cell (no fixed locations0


certain chromosomes have a tendency to occupy neighboring ___


chromosomes appear to be anchored in place by their centromeres


within each ___, chromosomes are dynamic and chromosome loops can be seen to change position


location of a specific chromosome region within a __ depends on when it is replicated and whether it is transcribed

late replicating regions

tend to occur near the nuclear envelope

early replicating regions

tend to occur near the nucleus center

interchromosome domains

provides space for proteins and mRNA


transcriptionally active regions tend to occur at territory interfaces

Chromatin Conformation Capture (3C)

can be used to identify inter- and intra- chromosomal interactions

The diameter of a chromosome territory is approximately equal to which of the following?

1 micro meter

point centromeres

are defined by specific DNA sequences (CEN) which bind directly to the kinetochore

CEN sequences are ~120 bp long


contain conserved sequences that attach to single microtubules

Regional centromeres

more diffused and are defined by epigenetic modifications


most common forms


made up of heterochromatin


are more variable and can attach to multiple microtubules

holocentric

when entire chromosomes function as centromeres


in a few organisms

CENP-A

variant histone H3


human centromeres are defined by the presence of ___


mediated the attachment of the kinetochore to the centromere and allows the centromere to be self-replicating

Meiotic drive

a form of intragenomic conflict which occurs when certain DNA sequences obtain a transmission advantage during meiosis


leads to violations of Mendel's 1st law

selfish elements

driving alleles can spread even when they reduce individual fitness

one mechanism that can lead to meiotic drive

competition between centromeres for kinetochore proteins: stronger centromere sequences are preferentially segregated to the ovum


can negatively impact male fitness


can select for drive suppressors

monkeyflower Mimulus guttatus: centromere-associated drive

a driving allele D has a 58:42 advantage over non-driving alleles in female meiosis


homozygous individuals suffer reduced polled viability


D is maintained at an intermediate frequency of ~35% in some pop's

centromere paradox

although essential for segregation,centromeres and their associated proteins evolve rapidly


Thiscan be explained by meiotic drive. Driving alleles spread through a populationbecause they have a transmission advantage


However, because they reduce malefitness, this leads to selection for drive suppressors.

Which of the following processes is least likely to be associated withmeiotic drive?

cancer

telomeres purpose

1.Theyprotect the ends of linear chromosomes from DNA damage and damage repairmechanisms.


2.Theycompensate for incomplete DNA replication at chromosome ends.


Telomeres are composed of shortrepeats, telomericproteins (shelterin)and telomericRNAs (TERRA).


Human telomeres contain thousandsof telomericrepeats (TTAGGG) which decrease in size with age.

Hayflick limit

continues shortening of telomeres eventually leads to cell senescence

DNA damage response mechanisms (that telomeres protect chromosome ends from)

•double-strand break repair


•ssDNA-induced cell cycle arrest


•non-homologous end joining


•homologous recombination

Shelterin

acomplex of 6 proteins that cap the telomere

subtelomeres

rapidly evolving regions

subtelomeres

rapidly evolving regions that lie betweenthe telomericrepeats and the more stable chromosome-specific sequences in the core.


undergo frequent: •segmental duplication•rearrangement•recombination


Mosaic structure containing:•tandem repeats•pseudogenes•gene families•transposable elements

Subtelomeric genes

exhibit elevated levels of sequenceand copy number variation between individuals and species.


Thismay facilitate adaptation to changing environmental conditions, especially inhost-parasite interactions

subtelomeric location

can also affect expression throughproximity to telomericheterochromatin.

telomeric expression sites

only one of ~15 is active

Telomeric archieves

arrays of 100's of VSG genes and pseudogenes are contained in____

minichromosomes

are 50-100 kb long and have 1 VSG at each end

Gene conversion

copies inactive VSG genes from the subtelomeric arrays into the active expression sites

Reciprocal telomere

exchange (recombination) moves VSG genes from the ends of the minichromosomes into the expression sites

mosaic gene conversion

can assemble novel VSG genes n the expression sites

Which of the following would you expect to find in a subtelomere?

telomeric repeats and immunoglobulin genes (no histone genes)