Lecture #22 Nuclear Structure and Organization

21,000

How many proteins coding genes do humans have?

6

How many ft of DNA do humans have?

1.5

Only about ____ percent of human DNA encodes proteins and functional RNAs

45

•About _____ percent of human DNA is derived from mobile DNA elements, genetic symbionts that have contributed to the evolution of contemporary genomes.

Gene

the entire nucleic acid sequence that is necessary for the synthesis of a functional gene product (polypeptide or RNA) - protein coding, enhancer, and promoter regions

Solitary genes

•25-50 percent of the protein-coding genes in multicellular organisms are represented only once in the haploid genome.

solitary, gene family

•Protein-coding genes may be _____ or belong to a ____

simple transcription unit

•A monocistronic region extending from the 5′ cap site to the 3′ poly(A) site with introns removed that encodes one protein

Complex transcription units

Primary transcripts can be processed in alternative ways:

Retrotransposons, transposons

•Promote the generation of gene families by gene duplication

more

Duplicated genes: ____ common in higher eukaryotes

higher

Lower eukaryotes have a _____ density of protein-coding genes without introns.

Redundancy

duplicate gene retains its function and increase basal transcript levels

Neofunctionalization

•duplicated genes tend to accumulate mutations faster and these mutations may result in new and different functions.

Subfunctionalization

•Mutation in both copies of the gene lead to functionality of the original gene become distributed among the two copies.

gene loss or pseudogene

The extra copy of the gene may be lost over time due to not being needed, or it may become a __ (the copy of the gene is retained but mutations lead to nonfunctionality).

homologous genes

all evolved from common ancestor

orthologous genes

•same function but differ as a result of speciation

paralogous genes

differ as a result of gene duplication

unknown

Majority of genes are of _____ function

Nucleosome

DNA wrapped around the histone octamer

10nm nucleosome filament

"beads on a string": nucleosomes linked together by DNA strand

Nucleosome, 10nm nucleosome filament, 30 nm fibers, supercoiled DNA loops, condensed mitotic chromosome

Order of chromatin condensing

histones

-The protein component of chromosomes include ____ a group of highly conserved proteins.

+

Histones are what charge

chromatin fibers

•Chromosomes consist of _____, composed of DNA and associated proteins.

linker DNA

•Each nucleosome is joined by a short stretch of ____ Length varies up to about 80bp

histone octamer

•Each consists of eight histone subunit proteins: the _____

1.7

•And 147bp of DNA that makes ____ turns around this core histone assembly

Histone octamer

•2 molecules each of histone H2A, H2B, H3 and H4 that adopts a disc shape around which the 147bp coil always in a left-handed turn

H2A, H2B, H3, H4

4 major subunits that are duplicated in histone octamer

lysine

•All 4 histone proteins are small with a large number of positively charged _____ residues that promote tight association with the negatively charged DNA sugar-phosphate backbone

N-terminal amino acid tail

•Each histone has a long, unstructured ____ that extends out from the nucleosome

histone H1

-A 30-nm filament is another level of chromatin packaging, maintained by ____

noncovalent

•DNA and histones are held together by _____ bonds.

Ionic

____bonds between negatively charged phosphates of the DNA backbone and positively charged residues of the histones.

Chromatin-remodeling complexes

•Hydrolyze ATP and use this energy to slide DNA associated with octamers in order to regulate compaction

Histone code

specific post-translational modification combinations in different chromatin regions specifically influence chromatin function by creating or removing chromatin-associated protein binding sites

Acetylation, phosphorylation, methylation, ubiquitination

4 key histone tail modifications

Acetylation of lysines

•for example, neutralize their positive charge, weakening histone/DNA associations, thereby making DNA more accessible

Methylation

will prevent acetylation, resulting in more compact DNA not as accessible for transcription.

heterochromatin

•Most highly condensed interphase chromatin is called ______ - essentially inactive and without transcription

centromere, telomeres

Heterochromatin is Concentrated around the center (____) and termini (-____) of chromosomes. With variable regions interspersed along the length.

Euchromatin, active

•Variable state of decondensed chromatin, some more relaxed than other, transcriptionally _____ regions of chromosome

Heterochromatin

Methylation of lysine 9 in histone H3 (H3K9me) is principle factor establishing _____

Epigenetic

regulation depends on factors other than DNA sequence

Epigenetic modifications

can be transmitted from parent to progeny cells and regulate gene expression without altering nucleotide sequence

X chromosome inactivation

Example of epigenetic inheritance

homologous

•Most cells of humans are diploid: contain one maternal and one paternal copy of each chromosome: _____ chromosomes

centromere

•The _____ is located at the site markedly indented on a chromosome.

constitutive heterochromatin

centromeres contain ______

telomere

•The end of each chromosome is called a _____and is distinguished by a set of repeated sequences.

telomerase

•New repeats are added by a _____ a reverse transcriptase that synthesizes DNA from a RNA template.