Lecture 22- Nuclear Structure and Chromatin Organization

Slide 33

DNA molecule

Each chromosome consists of a single __________, organized into increasing levels of condensation from nucleosomes to higher order chromatin folding by histone and nonhistone proteins.

Gene families

_________ arise from gene duplication during unequal meiosis recombination.

translated

Many genes encode functional RNAs that are not _________ into proteins but perform significant functions, such as rRNA, tRNA, and snRNA.

1.5

Only _____% of human DNA encodes proteins (directly) and functional RNA’s

mobile

About 45 percent of human DNA is derived from ______ DNA elements, genetic symbionts that have contributed to the evolution of contemporary genomes.

regulatory sequences

The nonencoding portion of eukaryotic DNA includes __________ that control gene expression and introns

Gene

the entire nucleic acid sequence that is necessary for the synthesis of a functional gene product (polypeptide or RNA)

Gene

has protein coding, enhancer, and promoter regions​ (with repeats of exons separated by introns)

Protein-coding

__________ genes may be solitary or belong to a gene family.​

Gene families

What encodes different proteins that have specific, but similar physiological functions ​(Heavily used gene products that must be transcribed at high rates)?

Solitary genes

What are the 25-50% of protein-coding genes that are represented only once in the haploid genome (unrelated to any other genes) called?

RNAs

Thousands of genes are transcribed into nonprotein-coding ______ for various known and unknown functions. ​

Simple transcription unit ​

(~10% of human transcripts) A monocistronic region extending from the 5′ cap site to the 3′ poly(A) site with introns removed that encodes one protein​

Complex transcription unit

Primary transcripts that can be processed in alternative ways:​

• mRNAs with the same 5′ and 3′ exons but different internal exons

• alternative 3′ exons

• alternative cell type-specific promoters (f or g) yield mRNA1 in one cell type in which f is activated with a first exon (1A) different from the first exon in mRNA2 produced in a different cell type in which g is activated (and in which exon 1B is used)

repeated domains​

Protein-coding genes with repeats of similar exons separated by introns encode proteins that have ___________

unequal crossing

Protein-coding genes with repeats of similar exons separated by introns: evolved by tandem duplication of the repeated exon DNA, probably by _________ over during meiosis

mobile DNA elements

include transposons and retrotransposons

mobile DNA elements

Promote the generation of gene families by gene duplication​and rearrangement.

shuffling

exon ________ by mobile DNA elements creates new versions of genes

0.05

Less than _______% of mobile DNA elements in the human genome are still active and the rest are highly selective

duplication

Exon ________ is caused by unequal crossing over during meiosis → creates genetic diversity

Unequal

_______ recombination between elements and subsequent independent mutations yield duplicated genes on one chromosome that might encode slightly different proteins.​

higher

Duplicated genes are more common in ______ eukaryotes​

duplications

The different β-like globin genes arose by duplication of an ancestral gene, followed by repeated gene ________ and subsequent sequence drift and selection. ​

different

All the encoded hemoglobin proteins carry oxygen in the blood, but they exhibit _________ properties for specific physiological functions.​

introns

Lower eukaryotes have a higher density of protein-coding genes without ______. ​

duplication

Gene ________ can result in different outcomes:​

1. redundancy

2. neofunctionalization

3. subfunctionalization

4. gene loss or pseudogene

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 be retained but mutations lead to nonfunctionality

homologous genes

Genes that evolved from a common ancestor (ex: tubulins)

orthologous genes

genes with the same function that differ as a result of speciation​ (same genes in different organisms)

paralogous genes

genes that differ as a result of gene duplication (different genes in the same orgainsm/ex: alpha and beta-tubulin)

No

Is biological complexity is directly related to the number of protein-coding genes?

50

About ____% of human genes are of unknown function

Chromatin

_______ contains nucleosomes of DNA wrapped around histone octamers.

Histone tail

________ modifications regulate chromatin structure, X-chromosome inactivation, and gene transcription.​

Nucleosome

DNA wrapped around the histone octamer​

10 nm nucleosome filament

“beads on a string”: nucleosomes linked together by DNA strand

chromatin

Chromosomes consist of ______ fibers, composed of DNA and associated proteins.​

chromosome

Each __________ contains a single, continuous DNA molecule.

Nucleosomes

The Lowest Level of Chromosome Organization​

Nucleosomes

The protein component of chromosomes include histones, a group of highly conserved proteins.​

amino acids

Histones have a high content of basic _________ (positive charge).​

linker DNA

Each nucleosome is joined by a short stretch of ___________: Length varies up to about 80bp​

1.7

How many turns does DNA make around the core histone assembly?

histone octamer

The 8 histone subunit proteins makes up the…

H2A, H2B, H3 and H4

Histone octamer: 2 molecules each of histone __________ that adopts a disc shape around which the 147bp coil always in a left-handed turn

lysine residues

All 4 histone proteins are small with a large number of positively charged _________ 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​ (These play an important role in regulating higher order of packing)

conserved

The histone’s N-terminal amino acid tail’s function and therefore structure and sequence are so deeply __________ that there are only 2 amino acid differences in the H4 protein between humans and pea plants.​

nucleosome

Each “bead” in higher order packing is…

H1

A fifth histone protein (__) binds linker DNA and the DNA wrapped around the octamer. ​

linker DNA

Each “line” in higher order packing is…

H1

Higher Level of Chromatin Structure: A 30-nm filament is another level of chromatin packaging, maintained by histone ___.​

Chromatin

__________ filaments are organized into large supercoiled loops.​

nucleosomes

Histone modification is one mechanism to alter the character of ___________.​

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.​

enzymes

Histones, regulatory proteins, and _________ dynamically mediate DNA transcription, compaction, replication, recombination, and repair.​

Chromatin-remodeling complexes

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

octamers

Making chromatin more or less compact promotes the expulsion or inclusion of ___________ or the exchange of many histone protein variants​.

acetylation, methylation, phosphorylation, and ubiquitination

Modifications of histone tails by ______,_________,____________,________ control chromatin condensation and function. ​

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

________ of lysines, for example, neutralize histone’s 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.​

silencing or​ expression

Depending on the residue, the specific histone protein and the specific covalent modification these​ changes may either compact or​ loosen chromatin, thereby​ promoting gene __________, respectively.

enzymes

Specific _________ (methytransferases, acetylase, deacetylases for example) are tightly controlled in order to regionally control chromatin configuration leading to the activation/inactivation of only specific genes.​

heterochromatin

Most highly condensed interphase chromatin is called __________ – essentially inactive and without transcription​

Heterochromatin

____________ is concentrated around the center (centromere) and termini (telomeres) of chromosomes. With variable regions interspersed along the length.​

Euchromatin

Variable state of decondensed chromatin, some more relaxed than other, transcriptionally active regions of chromosome​

Heterochromatin

Methylation of lysine 9 in histone H3 (H3K9me) is principle factor establishing heterochromatin. ​

H3K9me

_____ promotes heterochromatin spreading by recruiting specific methyltransferases that modify adjacent nucleosomes​ (will continue to spread until it encounters a barrier DNA sequence—boundary element)

Methylation

________ allows association with other histone-bound molecules to form tight assembleges of DNA

boundary element

The spreading process from methylation continues until it encounters a “______________” where several nonhistone proteins are bound to the DNA.​

Yes

Does epigenetic regulation depends on factors other than DNA sequence​?

altering

Epigenetic modifications can be transmitted from parent to progeny cells and regulate gene expression without ________ nucleotide sequence​ (preserves patterns of heterochromatin)

epigenetic modifications

X-chromosome inactivation is an example of ______________, since the two X chromosomes can have identical DNA sequences, but one is inactivated and the other is not.​

homologous chromosomes

Most cells of humans are diploid: contain one maternal and one paternal copy of each chromosome: ______________​

transcription factories

Genes (euchromatin) are physically moved to nuclear sites called ___________ where transcription machinery is located.​

Centromere

Contain constitutive heterochromatin, the site of microtubule attachment during mitosis, and DNA is not important for its structure and function (never accessible)

telomere

The end of each chromosome is called a ________ and is distinguished by a set of repeated sequences.​

telomerase

Because there is no primer for the end of the lagging strand, new repeats to telomeres are added by a __________, a reverse transcriptase that synthesizes DNA from a RNA template.​

Telomeres

________ are required for the complete replication of the chromosome because they protect the ends from being degraded.​

somatic

In ________ cells, telomere lengths are reduced each cell division to limit cell doublings.​

senescence

A critical point that occurs from telomere shortening when cells stop their growth and division​

proliferate

Cells like stem cells are able to resume telomerase expression after senescence and continue to _______

tumors

Most cells do not express telomerase → Approximately 90% of human _______ have cells with active telomerase