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DevBio Ch03 Part1

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Chapter 3.

Differential gene expression-Mechanism of cell differentiation

Based on the basic assumtion, “Genomic equivalence”,


scientist have asked “ how nuclear genes can direct
development when these genes are exactly the same in every
cell type?”

The answers are


1.Differential gene expression
2.Selective nuclear RNA processing
3.Selective messenger RNA translation
4.Differential protein modification
Chapter 3 Opener
Figure 3.1 The central dogma of biology
Figure 3.2 Gene expression (Part 2)
Figure 3.2 Gene expression (Part 3)
Figure 2.1 Cloning a mammal using nuclei from adult somatic cells

Evidence for genetic equivalence


-Nuclear transfer and cloning of frog(1952,
Briggs and King)
-Nuclear transfer from adult frog(1975,
Gurdon et al.)
-Nuclear transfer in sheep(1997, Wilmut)
Figure 2.2 The kitten “CC” (From 9 th Edition)

Resurrection is not possible!


Figure 2.2 Nucleosome and chromatin structure (Part 2)
Figure 2.2 Nucleosome and chromatin structure (Part 3)
Figure 2.4 Nucleotide sequence of the human -globin gene (Part 1)
Figure 2.4 Nucleotide sequence of the human -globin gene (Part 2)
Figure 2.5 Steps in the production of -globin and hemoglobin
Figure 2.6 The bridge between enhancer and promoter can be made by transcription factors
Figure 2.7 The role of the Mediator complex in forming the transcription pre-initiation complex
(Part 1)

-Mediator complex links the enhancer and promoter


to form the initiation complex
Figure 2.7 The role of the Mediator complex in forming the transcription pre-initiation complex
(Part 2)

-Mediator complex links the enhancer and promoter


to form the initiation complex
Figure 2.8 The genetic elements regulating tissue-specific transcription can be identified by fusing
reporter genes to suspected enhancer regions of the genes expressed in particular cell types
(Part 1)
Figure 2.8 The genetic elements regulating tissue-specific transcription can be identified by fusing
reporter genes to suspected enhancer regions of the genes expressed in particular cell types
(Part 2)
Figure 2.9 Enhancer region modularity

-Enhancer region may have multiple


modules for differential gene expression

-Each module may need combinatorial


association with specific transcription
factors for the gene expression
Figure 2.9 Enhancer region modularity (Part 1)

-Enhancer region may have multiple modules for differential gene expression
Figure 2.9 Enhancer region modularity (Part 2)

- Each enhancer module is regulated by combinatorial


actions of several transcription factors
Figure 2.10 Modular transcriptional regulatory regions using Pax6 as an activator

- Each enhancer module is regulated by combinatorial


actions of several transcription factors
Figure 2.13 A silencer represses gene transcription (Neuron-Restrictive Silencer Element)
Figure 2.11 Three-dimensional model of the homodimeric transcription factor MITF (one protein
shown in red, the other in blue) binding to a promoter element in DNA (white)
Table 2.1 Some major transcription factor families and subfamilies

- Pioneer transcription factor: open up the repressed chromatin and maintain


activation status
- Master regulator: 1) expressed at the beginning of cell type specification, 2)
Regulate many cell type specific genes, 3) can change cell fate.
- Oct4, c-Myc, Sox2, Klf4…. Yamanaka factors are examples of master
regulators
Figure 3.14 From differentiated fibroblast to induced pluripotent stem cell with four transcription
factors
Figure 3.15 Pancreatic lineage, transcription factors, and direct conversion of β cells to treat
diabetes (Part 1)

Specific combination of transcription factors can switch cell types!!


Figure 3.15 Pancreatic lineage, transcription factors, and direct conversion of β cells to treat
diabetes (Part 2)
Figure 3.16 Gene regulatory networks of endodermal lineages in the sea urchin embryo (Part 1)
Mechanism of Differential Gene Transcription
Figure 2.2 Nucleosome and chromatin structure (Part 4)
Figure 2.3 Histone methylations on histone H3
Figure 2.16 Methylation of globin genes in human embryonic blood cells (Part 1)
Figure 2.16 Methylation of globin genes in human embryonic blood cells (Part 2)
Figure 2.17 DNA methylation can block transcription by preventing transcription factors from
binding to the enhancer region
Figure 2.18 Modifying nucleosomes through methylated DNA (Part 1)
Figure 2.18 Modifying nucleosomes through methylated DNA (Part 2)
Figure 2.15 Chromatin regulation in HCPs and LCPs (Part 1)

Promoters can exist in three major


states: an active state, a repressed
state, and an intermediate, or “poised”
state

HCPs are usually found in


developmental control genes such as
transcription factors

HCPs are usually not methylated.

The default status of HCPs are Open


chromatin and the elongation is critical
step for gene expression
Figure 2.21 Model for the regulation of RNA elongation by the Mediator protein Med26

- The elongation is critical step for gene expression


Figure 2.15 Chromatin regulation in HCPs and LCPs (Part 2)

LCPs are Usually found in those genes


whose products characterize mature
cells (e.g., globins in RBC)
Active
LCPs are usually methylated

The default status of LCPs is inactive


form. A specific transcription factor can
initiate the gene expression.

Poised
(intermediate
state)

Inactive
Figure 2.20 Regulation of the imprinted Igf2 gene in the mouse

Genomic imprinting: Differential expression of maternal and paternal genes


Figure 2.23 Inheritance patterns for Prader-Willi and Angelman syndromes
Figure 2.2 The kitten “CC” (From 9 th Edition)

Resurrection is not possible!

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