1. Gene expression regulation
Chapter 18
Gene expression regulation
Enmin Li

2. 20500
gene
犀利哥

3. The basic concept and character of gene expression regulation
Section 1
The basic concept and character of gene expression regulation
Chapter 18

4. 本节学习目标 三个基本概念：基因，基因表达，基 因表达调控 基因表达的时空特异性 顺式作用元件的本质特征 反式作用因子的本质特征
基因表达调控的意义

5. The concept of gene expression一
The concept of gene expression + =
gene expression
transcription
translation
DNA  RNA  Protein
transcription
DNA  RNA =
gene expression
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6. Interaction among large biomolecules
Key point
Interaction among large biomolecules TF
mRNA TF 5’
RNA pol TF TF
DNA TF
RNA
Protein
DNA  RNA
mRNA  Protein

7. The temporal-spatial specificity二
The temporal-spatial specificity
of gene expression
357

8. AFP (甲胎蛋白， alpha fetal protein)
The temporal specificity of gene expression
Some genes in genome are expressed in order of specific time
AFP (甲胎蛋白， alpha fetal protein)
4q13.3
hepatoma
10 mg/ml blood
16-20 week
3-4 mg/ml blood
health adult
0 mg/ml blood
Transcription
Promoter
Coding region

9. 补充资料
Summary of AFP
This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatoma or teratoma. However, hereditary persistence of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly.

10. The spatial specificity of gene expression
Isoform-specific expression pattern of desmosomal cadherins in the epidermis.
(Green et al., J Invest Dermatol 2007 )
DSC3
DSC2
DSC1
DSG1
DSG4
DSG3
DSG2
18q

12. 补充资料
Summary of DSC1
The protein encoded by this gene is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family members, along with the desmogleins, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation. A subtype of IgA pemphigus, a life-threatening autoimmune disease, is characterized by the presence of autoantibodies that target the encoded protein. The desmosomal family members are arranged in two clusters on chromosome 18. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature protein. 

13. 补充资料
Summary of DSC2
This gene encodes a member of the desmocollin protein subfamily. Desmocollins, along with desmogleins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmocollin family members on chromosome 18. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia-11, and reduced protein expression has been described in several types of cancer. Alternative splicing results in multiple transcript variants.

14. 补充资料
Summary of DSC3
The protein encoded by this gene is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family members, along with the desmogleins, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation. The desmosomal family members are arranged in two clusters on chromosome 18, occupying less than 650 kb combined. Mutations in this gene are a cause of hypotrichosis and recurrent skin vesicles disorder. The protein can act as an autoantigen in pemphigus diseases, and it is also considered to be a biomarker for some cancers. Alternative splicing of this gene results in multiple transcript variants.

15. 补充资料
Summary of DSG1
This gene encodes a member of the desmoglein protein subfamily. Desmogleins, along with desmocollins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmoglein family members on chromosome 18. The encoded protein has been identified as a target of auto-antibodies in the autoimmune skin blistering disease pemphigus foliaceus. Disruption of this gene has also been associated with the skin diseases palmoplantar keratoderma and erythroderma.

16. 补充资料
Summary of DSG2
This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. Mutations in this gene have been associated with arrhythmogenic right ventricular dysplasia, familial, 10.

17. 补充资料
Summary of DSG3
This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. The encoded protein has been identified as the autoantigen of the autoimmune blistering disease pemphigus vulgaris.

18. 补充资料
Summary of DSC4
This gene encodes a member of the desmoglein subgroup of desmosomal cadherins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a transmembrane component of desmosomes and may play a role in cell-cell adhesion in epithelial cells. Mutations in the gene are associated with localized autosomal recessive hypotrichosis and monilethrix, characterized by impaired hair growth.

19. Modality of gene expression三
Modality of gene expression
Constitutive gene expression
Inductive and repressive gene expression
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20. Constitutive gene expression -actin is housekeeping gene
housekeeping genes
1937, TCA cycle
1953, Nobel Prize
9 enzymes or enzyme complex are housekeeping genes in tricarboxylic acid cycle
Our lab’s result
-actin
-actin is housekeeping gene
Hans Adolf Krebs

21. 一项国家自然科学基金项目 NGAL 项目名称：食管癌中NGAL 与LOXL2功能复合物系统鉴 定及其分子作用机制研究 项目负责人：吴炳礼博士
项目执行时间：
项目经费：68万元
谢谢各位专家。
NGAL

22. Inductive and repressive gene expression
represive signals
activated signals
receptors
mRNA
Protein

23. Cis-acting elements and trans-acting factors四
Cis-acting elements and trans-acting factors
358

24. cis-acting elements trans-acting factors intron exon RNA pol Ⅱ
poly A site
AATAAA, 30bp
Initiation site
intron
intron
silencer
upstream
silencer
downstream
enhancers
ATG
TAA
coding strand 5 3 1 1 2 2
n-1 n
template strand
upstream
enhancers
promoter
exon
terminator
downstream
silencer
intron
enhancer
CCAAT box
GC box
TATA box

25. Cis-acting elements
Trans-acting factors

26. Multilevel regulation of gene expression五
Multilevel regulation of gene expression
359

27. initiation of RNA transcription*
Key point
activity of gene structure in genome
DNA amplification
DNA rearrangement
DNA methylation
initiation of RNA transcription*
process of RNA post-transcription
transport of RNA post-processing
initiation of protein translation 1 + 2
DNA 5
transcription
pre-mRNA 6
RNA process
mRNA 7
transport
translation 8
protein

28. Biological significance of gene expression regulation六
Biological significance of gene expression regulation
359

29. 1 2
acclimation
cell growth and proliferation
monocellular
organisms
1+2
multicellular
organisms 3 4
cell differentiation
individual development

30. Thank you
谢谢各位专家。

31. 谢谢各位专家。