Developmental gene regulation

Question 1

Waddington’s epigenetic landscape

Answer 1

cell fate during development is regulated epigenetically by genes being turned off and on at the right place and time

Question 2

Genetic control of cell identity in muscle regeneration

Answer 2

3 TF are active at different stages; Pax7 - MyoD; MyoD - Myog,
Myog is a MyoD target gene, but Myod is not sufficient to activate Myog,
Integration of intrinsic and extrinsic cues ensures that developmental genes are activated in the correct cells at the correct time

Question 3

Morphegens

Answer 3

signalling molecules that specify cell fate in a concentration-dependent manner, Made in specific sites in the embryo and diffuse over long distances to form a concentration gradient (highest at synthesis site), Regulate developmental transcription factors

Question 4

Morphogen regulation of MyoD/Myf5

Answer 4

Wnt signals (secreted by the dorsal neural tube) work in combination with Shh (secreted by the notochord and floor plate of the neural tube) to promote the stable expression of MyoD and Myf5 in the somite, the signals that induce MyoD and Myf5 are transient because the myogenic bHLH proteins can activate their own expression, transient signalling leads to stable cell type specification

Question 5

Transient signals

Answer 5

lead to stable cell type specification

Question 6

Wnt secreted by

Answer 6

dorsal neural tube

Question 7

Shh secreted by

Answer 7

notochord and floor plate of neural tube

Question 8

Myogenic bHLH proteins

Answer 8

can activate their own expression

Question 9

How are genes activated during development

Answer 9

genes need to go from repressed to active (or vice versa) when cells differentiate

Question 10

Key steps that must happen when cells differentiate

Answer 10

evict polycomb proteins, erase H3K27me3, write H3K4me3, write H3/H4-ac, recruit GTFs and RNA II, transcribe gene - order and proteins involved determined by the histone code

Question 11

Trithorax

Answer 11

Transcriptional activation (H3H4me3 readers)

Question 12

Polycomb

Answer 12

transcriptional repression (H3K27me3 readers)

Question 13

H3K27me3 writer

Answer 13

Ezh2 (polycomb)

Question 14

H3K27me3 eraser

Answer 14

UTX

Question 15

H3/H4-ac writers

Answer 15

KATs (PCAF and p300)

Question 16

H3K4me3 readers

Answer 16

proteins with bromofomains

Question 17

H3K4me3 writers

Answer 17

Ash2I/MLL2 (trithorax)

Question 18

H3K4me3 readers

Answer 18

TFIID and many more

Question 19

MyoD

Answer 19

helps recruit proteins that reshape the chromatin landscape, converting inactive chromatin to active chromatin

Question 20

TFIID

Answer 20

GTF that binds promoter DNA; interaction stabilized by histone binding, has bromodomains to bind acetylated histones and binds H3K4me3, then TFIID recruits other GTFs and RNA polI, RNA pol II pauses just after the promoter and must be released to the gene to be expressed

Question 21

NELF

Answer 21

Negative elongation factor, pauses RNA pol II

Question 22

Brd4

Answer 22

binds acetylated histones; its partner CDK9 phosphorylates CDT and NELF allowing elongation, only now is the gene transcribed

Question 23

Activation of the myogenin enhancer

Answer 23

A. enhancer is inactive (H3K27me3)
B. Six4 recruits UTX to demethylate H3K27; MyoD recruits p300/PCAF to acetylate histones (helps GFTs bind)
C. Phospho-MEF2D recruits Ash2I to methylate H3K4 (helps GFTs bind)
D. MyoD recruits P-TEFb, which allows Pol II to elongate; UTX carried down the gene by Pol II to remove remaining H3K27me3 throughout the gene

Question 24

Intrinsic

Answer 24

cell type specific TFs like Six4 and MyoD

Question 25

Extrinsic

Answer 25

signals from other cells required to activate MEF2 (Activated by p38 signalling

Question 26

Locomotion and timing

Answer 26

spatiotemporal control, cells need to know where they are within the embyo and when to divide, differentiate, migrate (controlled by morphogens)

Question 27

How do cells know their identity anf fates

Answer 27

Cell identity and fate are regulated by the combined effects of cell signals and transcription factors

Question 28

example of cell identity

Answer 28

Tbx6 is a transcription factor necessary for paxial mesoderm identity, when it's deleted, cells that would form paxial mesoderm make extra neural tubes instead ( indicated by expression of Sox2) Even ectopic neural tube cells know where they are in the embryo: they correctly express the Pax6 on dorsal side because of morphogens

Question 29

How do cells know their location in the embryo

Answer 29

morphogens: signalling molecules that specify cell fate in a concentration-dependent manner, made in specific sites in the embryo and diffuse over long distances to form a concentration gradient (highest at synthesis site), and regulate developmental transcription factors

Question 30

Neural tube

Answer 30

nervous system

Question 31

Intermediate mesoderm

Answer 31

kidneys and gonads

Question 32

Lateral plate mesoderm

Answer 32

circulatory system, somatic

Question 33

paraxial mesoderm

Answer 33

head somite (muscles, tendons, cartilage)

Question 34

Embryonic sources of organs

Answer 34

Many embryonic structures exist only during development, the structures contain stem/progenitor cells that give rise to organs, cells in these structures also produce signals to guide cell differentiation and migration (provide regional information (dorsal, ventral, anterior, posterior)