Cell Biology Exam 4: Chapter 12 pt.2

The Cell Nucleus and the Control of Gene Expression

the DNA in the nucleus exists in what two forms that reflect the level of activity of the cell

• euchromatin

• heterochromatin

euchromatin (how packed is it, how does it appear, what cells is it prevalent in)

• lightly packed form of chromatin (DNA, RNA, & protein) that is rich in gene concentration and is often (but not always) under active transcription

• appears a small, darkly staining, irregular particles scattered throughout the nucleus or accumulated adjacent to the nuclear envelope

• prevalent in cells that are active in the transcription of many of their genes

heterochromatin (how packed is it, where is it dispersed, what cells is it prevalent in)

• tightly packed form of DNA

• dispersed throughout nucleus and not readily stainable

• most abundant in cells that are less active or not active

functions of heterochromatin

• gene regulation

• protects the integrity of chromosome/genome since it is tightly packed

euchromatin (what it is, and what percentage)

• most active portion of the genome in cells

• 92% of human chromosomes

euchromatin after mitosis

returns to a dispersed state

heterochromatin during mitosis

of 2 varieties & is condensed during interphase so that when cells divide they have an entire set of chromosomes

2 types of heterochromatin

• constitutive heterochromatin

• facultative heterochromatin

constitutive heterochromatin (how it is, where is it found, what does it conisist of)

• remains condensed all the time

• found mostly around centromeres and telomeres

• consists of highly repeated sequences and few genes

facultative heterochromatin (how is it, where it it found)

• is inactivated during certain phases of the organism’s life

• is found in one of the X chromosomes as a Barr body through X inactivation

• X inactivation is a random process, making adult females genetic mosaics

Barr body

• an inactive, condensed X chromosome found in the nucleus of female mammal cells.

• Because females have two X chromosomes (XX) but only need one, the body deactivates the extra one during development to prevent excessive genetic information, creating a small "clump" known as a Barr body.

purpose of Barr body

• regulate the # of X-linked genes being produced

• balance between X-linked genes between males and females

dosage compensation

an epigenetic mechanism that equalizes the expression of X-linked genes between males (typically XY) and females (XX) to prevent lethal gene dosage imbalances

how does consitutive heterochromatin play a role in the expression of genes

can affect the genes near them (position-effect variegation)

how does facultative heterochromatin play a role in gene expression

the result of genes that are silenced through a mechanism such as histone deacetylation or siRNA through RNAi

Calico cat cloning

random inactivation of the X chromosome in different cells during embryonic development creates a mosaic of tissue patches

Facultative heterochromatin: when is it inactivated

inactivated during certain phases of the organism’s life

Facultative heterochromatin: where is it found

found in one of the X chromosomes as a Barr body through X inactivation

X inactivation (describe the process & what it does)

a random process, making adult females genetic mosaics

Facultative heterochromatin: placental mammals XIST (what it stands for & what it does)

in placental mammals, the X-inactive specific transcript (XIST), and RNA gene on the X chromosome, acts as the major effector of the X inactivation process

histone code hypothesis

states that the activity of a chromatin region depends on the degree of chemical modification of histone tails

the 2 ways histone tail modifications influence chromatin

• serve as docking sites to recruit nonhistone proteins

• alter the way histones of neighboring nucleosomes interact

karyotyping

an ordered visual display of chromosomes arranged by size, shape, and banding pattern

what can karyotyping be from

• white blood cells

• fetal cells by amniocentesis or chorionic villus sampling

what may the pattern on karyotype be used for

to screen chromosomal abnormalities

down syndrome: what is it also called

trisomy 21

down syndrome: the condition, features, frequency, why it occurs

• an aneuploid condition resulting from three copies of chromosome 21

• characteristic facial features, short stature, heart defects, mental retardation

• frequency increases with age of mother

• occurs due to nondisjunction → abnormal chromosome separation

telomere

the end of each chromosome, distinguished by a set of repeated sequences

telomerase

adds new repeats, it is a reverse transcriptase that synthesizes DNA from and RNA template

what are telomeres required for & why

• the complete replication of the chromosome because they protect the ends from being degraded

• telomerase activity is thought to have major effects on cells life

the end-replication problem

generation of single stranded overhangs that shorten DNA

• the single-stranded overhang is not free but forms a loop

• the loop is a binding site for telomere-capping proteins that protect the ends of the chromosomes and regulate telomere length

telomeres in somatic cells

in somatic cells, telomere lengths are reduced each cell division to limit cell doublings

when does a critical point occur from telomere shortening

when cells stop their growth and division

what happens in cells that can resume telomerase expression

• they continue to proliferate

• these cells continue to divide and do not show normal signs of aging

telomerase: cancer

• 90% of human tumors have cells with active telomerase

• increase telomerase activity

• continuous abnormal growth

germ cells telomerase activity

maintain their telomerase activity throughout life, ensuring maximal telomerase length throughout life

skin, intestinal, and hemopoietic stem cells telomerase activity

ensure the continual production of differentiated cells

hereditary anaplastic anemia (what does the person have + why & what does this cause + why)

• the affected person has substantially reduced telomerase levels because of being heterozygous for the gene that encodes either the telomerase RNA or one of the protein subunits

• this causes bone marrow failure, because their hemopoietic tissue becomes unable to produce enough blood cells over a normal human lifetime

what is epigenetics

the study of how our behaviors & environmental factors can cause changes that impact how our genes are expressed

what does epigenetic inheritance depend on

factors other than DNA sequences

what is an example of epigenetic inheritance

X chromosome inactivation

X chromosome inactivation

the two X chromosomes can have identical DNA sequences, but one is inactivated while the other is not

an epigenetic state can be ______ & give an example

reversed, ex.) X chromosomes are reactivated prior to formation of gametes

epigenetics: identical twins, parental histones, heterochromatin, euchromatin

• differences in disease susceptibility and longevity between genetically identical twins may be due, in part, to epigenetic differences that appear between the twins as they age

• parental histones determine the chemical modifications found in the newly synthesized histones

• as heterochromatin is replicated, a histone methyltransferase labels the newly synthesized H3 molecules added into the daughter nucleosomes

• euchromatic regions tend to contain acetylated H3 tails, a modification transmitted from parental chromatin to progeny chromatin

transcription factories (what is moved here & what is located here)

genes are physically moved to nuclear sites called transcription factories where transcription machinery is located

what are the 4 chromosomal abberations and human disorders

• inversion

• translocations

• deletion

• duplication

chromosomal abberations and human disorders: inversion (what happens, does it cause problems, meiosis)

• chromosome breaks, turns 180 & reseals in a reverse order

• usually do not cause problems, but reverse sequence of alleles can lead to altered gene activity if it disrupts control of gene expression

• during meiosis, crossing-over can lead to recombinant chromosomes

chromosomal abberations and human disorders: translocations (what occurs, does it affect health, 2 syndromes)

• translocations are the result of attachments of all or one piece of one chromosome to another chromosome

• individual healthy except if it disrupts a gene

• 5% of down syndrome cases causes by translocation between chromosomes 14 & 21

• alagille syndrome translocation between chromosomes 2 & 20

what are 2 syndromes due to translocation

• 5% Down syndrome cases

• Alagille syndrome

5% down syndrome cases

translocation between chromosomes 14 & 21

Alagille syndrome

translocation between chromosomes 2 & 20

chromosomal abberations and human disorders: deletion (what happens, 2 syndromes)

• when a single break causes a chromosomes to lose an end or 2 breaks result in the loss of an internal segment (deletions results when there is a loss of a portion of a chromosome)

• williams syndrome - long arm of chromosome 7 loses a tiny end piece (~26 genes or more)

• cri du chat- chromosome 5 loses an end piece

williams syndrome

long arm of chromosome 7 loses a tiny end piece

cri du chat

chromosome 5 loses an end piece

what is Williams syndrome & what is it characterized by

• deletion

• rare neurodevelopmental disorder

• distinctive “elfin” facial appearances along with a low nasal bridge

• an unusually cheerful demeanor and ease with strangers (outgoing/sociable)

• developmental delay and learning disabilities

• cardiovascular problems

• strikingly strong language and music skills

• attention deficit disorder (ADD; easily distracted), problems with anxiety, and phobias

chromosomal abberations and human disorders: duplication (what occurs, what do the individuals have, syndrome)

• chromosome segment repeated

• individual has more than 2 alleles for certain traits

• inv dup 15 syndrome- inverted duplication of chromosome 15 (isodicentric 15)

• inversion- segment joins in direction opposite from normal

inv dup 15 syndrome

• inv dup 15 syndrome- inverted duplication of chromosome 15 (isodicentric 15)

• inversion → segment joins in direction opposite from normal

inv dup 15 syndrome (how many chromosomes, inheritance, & symptoms)

• 47 chromosomes instead of the normal 46

• generally not inherited, it appears de novo; in one member of family, by chance

symptoms

• delayed language development

• poor motor skills such as walking or sitting up

• low muscle tone (hypotonia), seizures, short stature, and intellectual disability

• distinctive facial features may include epicanthal folds (skin folds at the inner corners of the eyes), a flattened nasal bridge, button nose, and a high arches palate (roof of the mouth)

• some also have features of autism