复旦大学：《表观遗传学》（英文版）Genomes and gene number

观遗传鹭 Epigenetics Chromatin based gene control Chaoqun Wu School of Life Sciences, Fudan University 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 1 Epigenetics — Chromatin based gene control Chaoqun Wu School of Life Sciences, Fudan University

Genomes and gene number 600019,00013,50030,00027,000 Gene number 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 2 Genomes and Gene Number 6000 19,000 13,500 30,000 27,000 Gene number

Muscle cells But if in the same organIsm, should have the same DNA per Nerve cells( cell Different cells have different clusters of genes active Development and differentiation of embryos is controlled by signaling molecules that alter gene expression in cells 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 3 Muscle cells Nerve cells But if in the same organism, should have the same DNA per cell Different cells have different clusters of genes active Development and differentiation of embryos is controlled by signaling molecules that alter gene expression in cells

DNA and associated proteins(chromatin) nucleolus endoplasmic reticulum intermediate centrosome filaments microtubule nuclear pore nuclear lamina outer membrane nuclear envelope inner membrane 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 4

Genome is packaged into chromatin 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 5 Genome is packaged into chromatin

Basic unit is nucleosome: Consists of a core octamer of histones h2A H2B, H3 and H4 (2X). Approximately 150 bp DNA wrapped 2X around outside of nucleosome 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 6 Basic unit is nucleosome: Consists of a core octamer of histones H2A, H2B, H3 and H4 (2X). Approximately 150 bp DNA wrapped 2X around outside of nucleosome

Summary: the Regulation of Gene Expression in Eukaryotes NUCLEUSICYTOSOL protein translation activity control control primary RNA 3 4 transcript RNA R protein inactive protein transcriptional RNA control nuclear pore processing control nuclear envelope 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 7 Summary: the Regulation of Gene Expression in Eukaryotes

Dimerization activation of Transcription and translation CYTOPLASM Protein folding 米 Translation Nuclear localizatio mRNA export ( Initiation( Elongation (T Termination AAAooo 3 RNAP RNAPII mRNA packaging Transcript cleavage Ch 5 capping 3

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 8 Transcription and Translation

Cell-specific regulation of gene expression A specific signal molecule (such as one with the message, become a muscle cell )leads to production of regulatory proteins. These proteins bind to regulatory sites in DNA, triggering transcription of cell-specific proteins Promoter TRANSCRIPTION 0o00000000000000 Enhancer Exon Intron Exon Intron Exon Enhancer Promoter-proximal element 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 9 Cell-specific regulation of gene expression TRANSCRIPTION Enhancer Promoter Promoter-proximal element Enhancer A specific signal molecule (such as one with the message, “become a muscle cell”) leads to production of regulatory proteins. These proteins bind to regulatory sites in DNA, triggering transcription of cell-specific proteins. Exon Intron Exon Intron Exon

Transcription involves 4 types of proteins DNA-binding regulators Chromatin requlators Coactivators and corepressors Transcription apparatus Coactivator Chromatin regulators Mediator Transcription apparatus TEIIH RNAPII TFIF TFIE TFIIA TFIIB TFID DNA-binding requlators Gene 2005-11-11 Chaoqun Wu, Fudan University

2005-11-11 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 10 TFIIB RNAPII TFIIA TFIID TFIIH TFIIF Mediator TFIIE DNA-binding Regulators Transcription involves 4 types of proteins • DNA-binding regulators • Chromatin regulators • Coactivators and corepressors • Transcription apparatus Chromatin regulators Transcription apparatus Coactivator Gene