Cell And Developmental Flashcards

0
Q

Percentage components of chromatin

A

10% compact transcriptionally inactive heterochromatin

90%

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1
Q

What are Hox genes? + properties

A

-a group of related genes that control the body plan of an embryo along the anterior-posterior (head-tail) axis
-post embryonic segmentation
-Hox proteins determine the type of segment structures (e.g. legs, antennae) that will form on a given segment
-control segmental identity, but do not form the actual segments
-properties:
Protein product is a transcription factor
Contain homeobox DNA sequence
Genes organised in the same as the order of their expression (anterior-posterior axis of body) on the chromosome, thus said to display colinearity

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2
Q

Modifications to RNA

A

Poly A tail added
Splicing
Methalyinated cap

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3
Q

Histone modifications

A

Post translation modifications:

  • acetylation
  • methylation
  • phosphorylation
  • ubiquination
  • ADP ribosylation

Modifications alter the electro

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4
Q

Histone tail acetylation and deacetylation

A

Histone acetyl transferases (HATs) - add acetyl group - activation of gene expression
Histone deacetylases (HDACs) - removes acetyl group - repression of gene expression
Main acetylation include lysine residues 9, 14, 18 and 23
Deacetylasation - positive charge = tight electrostatic interaction between DNA and histones so transcription factors and RNA pol cannot bind.
Acetylasation - removes positive charge, therefore neutral = looser binding between DNA and histones.

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5
Q

Polytene Chromosomes

A

Chromosomes replicated without cell division
Found in drosophila salivary glands - required to provide large amount of glue proteins for pupation
Bright banding represents areas of transcriptional activity

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6
Q

X Chromosome inactivation

A

Female must have 2 copies of X chromosome
One copy must be silenced - example of dosage compensation
In placental mammals this is random, in marsupials the paternal X chromosome is always deactivated
Early in embryonic development one copy of the X chromosome is inactivated in each cell in female mammals
-Only one copy is transcribed
-Irreversible in somatic cell but is reversed in germ cell
Inactivation involves shortening and condensing of one X chromosome to form Barr body

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7
Q

What does the X chromosome encode?

A

Contains 1000 genes

Include genes encoding important proteins for growth and development

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8
Q

Can females develop X linked recessive diseases?

A

Do not usually display symptoms …

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9
Q

Dosage compensation in drosophila

A

Transcription of male X chromosome is doubled
Single male makes same amount of transcript as two female chromosomes
Achieved through acetylasation …

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10
Q

Histone methylation at specific lysine residues

A

?.

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11
Q

DNA Methylation

A

Addition of methyl group to cytosine base that is part of CpG dimers
Involved in initiation and maintenance of gene silencing
Targeted to certain regions of the genome (eg Repetitive DNA, transposable elements)
Promoters of housekeeping genes (expressed in all cells eg RNA polymerase) are hypomethylated and therefore transcriptionally active…

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12
Q

Define Epigenetics

A

The study of heritable changes in gene function that occur without a change in the sequence of the DNA

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13
Q

Discuss the role of homeotic genes in Drosophila embryo development

A

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14
Q

How are DNA methylation patterns inherited?

A

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15
Q

What are histone proteins and how can they be modified to regulate gene expression?

A

16
Q

How is the coat pattern of calico cats epigenetically regulated?

A

17
Q

How is the anterior-posterior axis established in Drosophila embryo development?

A

18
Q

CCK Signalling

A
  • Peptide secreted by the mucosal cells of the duodenum into bloodstream
  • secretion is increased when
  • CCK binds to its GPCR, activated associated heterotrimeric G protein
  • G protein activates effector (PLC)
19
Q

GPCRs

A

Large family - thousands known in mammals

20
Q

The CCK receptor structure

A

Single polypeptide

21
Q

What does PLC hydrolyse when activated?

A

PIP2 - a plasma membrane phosphoglyceride

Products of this are IP3 and DAG - intracellular second messengers

22
Q

IP3 Action

A
  • water soluble, diffuses into cytoplasm where it binds to receptor on ER
  • results in release of
23
Q

Pancreatitis

A

Disease that can be brought on by:

-migrating gallstones (through

24
Q

Discuss the role of protein kinases and phosphoprotein phosphatases in intracellular signalling

A

-2

25
Q

Why is drosophila used?

A
Easy to breed
—Tolerant of diverse conditions
—High fecundity
—Fast lifecycle, lab flies —
26 days (female)
—33 days (male)
Sequenced genome
26
Q

What are maternal effect genes?

A

Genes which, if mutated in mother, cause defects in the offspring.
-bicoid, nanos, caudal, hunchback
About 50 maternal genes are involved in setting up positional information in the egg
Prior to fertilisation
—Some proteins and mRNAs are localized at each end of the egg as it is formed in the ovary E.g. bicoid and nanos
—After development begins, maternal mRNAs are
translated
—The proteins that are produced regulate each other and zygotic genes in the nuclei of the embryo

27
Q

Bicoid protein

A

Early Drosophila development

  • a maternal effect gene
  • mRNA is located at the anterior pole
    —-After fertilisation bicoid mRNA is translated and the Bicoid protein diffuses to form a concentration gradient
  • ANTERIOR to POSTERIOR gradient
    —-Bifunctional protein:
    —Transcription factor: Bicoid influences fate (gene
    expression) in a concentration dependent manner (eg switches on zygotic hunchback by binding to regulatory sites on the hunchback promoter)
    —RNA binding protein: Bicoid inhibits the translation of caudal mRNA in the anterior part of the embryo resulting in an posterior to anterior gradient of Caudal protein
  • leads to the expression of zygotic gap genes
28
Q

Nanos protein

A

Drosophila development
-blocks Hunchback translation
nanos mRNA is localised to the posterior pole
—-After fertilisation Nanos protein diffuses throughout
the posterior part of the embryo
-POSTERIOR to ANTERIOR gradient
—-Nanos blocks the translation of maternal hunchback mRNA in the posterior part of the embryo
—-Anterior to posterior gradient of Hunchback protein

29
Q

What are gap genes?

A

A gap gene is a type of gene involved in the development of the segmented embryos of some arthropods. Gap genes are defined by the effect of a mutation in that gene, which causes the loss of contiguous body segments, resembling a gap in the normal body plan.
-hunchback, giant, KrÜppel, knirps, tailless

30
Q

Expression of gap genes

A
  • drosophila development
  • Bicoid expression leads to the expression of zygotic gap genes
    —-They are the first zygotic genes to be expressed along the anterior-posterior axis
    —-All gap genes encode transcription factors E.g. giant, Krüppel, knirps, tailless
    —-Gap proteins diffuse away from their site of synthesis (acellular embryo), but the proteins have very short half lives (minutes)
    —-Bell-shaped protein concentration profiles —
  • Zygotic Hunchback is the exception:
    —Expressed over a broad region producing a steep anterior-posterior gradient
31
Q

Hunchback expression

A

Drosophila development

  • A low level of maternal hunchback mRNA is present in the egg before fertilisation (This was laid down during oogenesis - egg formation)
    —-After fertilisation, Bicoid switches on zygotic hunchback
    —-This only happens when the concentration of Bicoid exceeds a threshold
    —-Bicoid is a transcription factor that binds to regulatory sites in the hunchback promoter
  • Increasing the amount of maternal bicoid increases the size of the domain of hunchback expression
32
Q

Kruppel expression

A

Drosophila development

  • Krüppel expression is activated by a combination of Bicoid and low levels of Hunchback
    —-Krüppel expression is repressed at high levels of Hunchback
  • wild type only expresses kruppel in centre of embryo - where there is both bicoid and low levels of hunchback (due to their diffusion gradients)
    —-In mutants lacking the bicoid gene zygotic hunchback expression does not occur and only maternal Hunchback protein is present
    —-This level of Hunchback is above the threshold for activation of Krüppel and below the threshold for repression, activating Krüppel throughout the anterior end of the embryo
    —-Similar threshold effects of Hunchback define the anterior borders of expression of knirps and giant
33
Q

How is the asymmetrical division of

A

Proteins localised at diff poles of cell:
-Plec localised at flagellulm
-DivJ localised at stalk
2 component signalling system
-response regulator = CtrA
In swarmer cells:
-PleC dephosphorylates DivK, allowing DivL to promote CckA kinase activity = phosphorylation of CtrA.
-CtrA activated
In stalked cells:
-DivJ phosphorylates DivK that then binds to DivL, inhibiting CckA kinase activity = dephosphorylation of CtrA.
-CtrA inactivated
In predivisional cells:
-CckA localizes with DivL and PleC at the swarmer pole, enabling CckA to escape downregulation by DivK∼P. Hence at the swarmer pole CckA acts as a kinase and CtrA is phosphorylated and active.