复旦大学：《表观遗传学》（英文版）Chromatin remodeling

廳遗 Epigenetics Chromatin based gene control Chaoqun Wu School of Life Sciences, Fudan University 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 1 Epigenetics — Chromatin based gene control Chaoqun Wu School of Life Sciences, Fudan University

Part v Chromatin remodeling 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 2 Part V. Chromatin remodeling

“香 一 Nucleosome 50 nm linker DNA core histones of nucleosome ○ DISSOCIATION TH A HIGH beads-on-a-string CONCENTRATION form of chromatin OF SALT includes 200 NUCLEASE DIGESTS nucleotide pairs LINKER DNA f DNA 8C2 ctameric histone core dNa double helix ISSOCIATION cle core particle H2A H2B H3 H4 Essential Cell Biology by alberts et al. 1997 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 3 Nucleosome Essential Cell Biology by Alberts et al. 1997

What is Chromatin remodeling Chromatin remodeling(染色质重构)isan important epigenetic mechanism Chemical modification of the protruding histone tails- by the addition of acetyl methyl or phosphate groups-can alter chromatin structure, which in turn influences the activity of adjacent genes 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 4 What is Chromatin remodeling Chromatin remodeling(染色质重构)is an important epigenetic mechanism. Chemical modification of the protruding histone tails — by the addition of acetyl, methyl or phosphate groups — can alter chromatin structure, which in turn influences the activity of adjacent genes

The remodeling of chromatin allows transcription factors to bind their cognate DNA Sites. Associated proteins with structural, modifying and/or transcriptional activities propagate and/or stabilize the actively transcribing chromatin structure leading to expression of the gene. The temporal order of interactions between cis and trans elements can vary 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 5 The remodeling of chromatin allows transcription factors to bind their cognate DNA sites. Associated proteins with structural, modifying and/or transcriptional activities propagate and/or stabilize the actively transcribing chromatin structure, leading to expression of the gene. The temporal order of interactions between cis and trans elements can vary

General model for gene regulation Chromatin Modifying Chromatin Remodeling RNA polymerase‖l Factors Factors holoenzyme Activators bind to specific DNA sequences DNa is packaged in higher order chromatin structure 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 6 General model for gene regulation RNA polymerase II holoenzyme Chromatin Modifying Factors Chromatin Remodeling Factors DNA is packaged in higher order chromatin structure Activators bind to specific DNA sequences

1. Nucleosome Positioning Nucleosome positioning is the phenomenon Where nucleosomes assume specific positions on a dNA molecule This position has two attributes a rotational setting a translational setting Nucleosomes have defined translational and rotational positions 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 7 1. Nucleosome Positioning • Nucleosome positioning is the phenomenon where nucleosomes assume specific positions on a DNA molecule • This position has two attributes: – a rotational setting – a translational setting • Nucleosomes have defined translational and rotational positions

a nucleosome can assume one of several different positions along a dNA molecule This is referred to as translational positioning Position Nucleosome DNA Position 2 Position 3 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 8 A nucleosome can assume one of several different positions along a DNA molecule This is referred to as translational positioning Nucleosome DNA Position 1 Position 2 Position 3

This causes certain cis-elements to be located in nucleosomes at positions where the trans-acting factors cannot recognize and bind to them There is therefore a requirement to make nucleosomally wrapped dNA of some gene promoters more accessible This is a function performed by the chromatin remodelers 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 9 •This causes certain cis-elements to be located in nucleosomes at positions where the trans-acting factors cannot recognize and bind to them • There is therefore a requirement to make nucleosomally wrapped DNA of some gene promoters more accessible • This is a function performed by the chromatin remodelers

2. Supposed remodeling steps Dissociation of h1 Acetylation and partial decondensation of the chromatin >recruitment of select transcriptional activators Which, in turn recruit Chromatin remodelers(染色质重构复合物) Additional histone modification enzymes The order of recruitment is not known 2005-10-29 Chaoqun Wu, Fudan University

2005-10-29 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 10 2. Supposed remodeling steps ¾ Dissociation of H1 ¾ Acetylation and partial decondensation of the chromatin ¾recruitment of select transcriptional activators, which, in turn, recruit • Chromatin remodelers(染色质重构复合物) • Additional histone modification enzymes • The order of recruitment is not known