BMS8110复习（十）：Lecture 10 - ChIP-seq Histone Modifications

Contents 

• Histone Modifications 组蛋白修饰
• Chromatin states 染色质状态
• ChromHMM: learning 'hidden' chromatin states
• Super-enhancers
• Bivalent promoters 二价启动子

Larger DNA structures mediate more compaction.

Euchromatin(常染色质): transcribed and less condensed.

Heterochromatin(异染色质): more condensed, genes silenced, replicate later in S phase.

结构上：
常染色质折叠压缩程度低，处于伸展状态；
异染色质折叠压缩程度高，处于聚缩状态。
功能上：
常染色质转录比较活跃；异染色质没有转录活性。

Histone Modifications and Modifiers

• Writers: enzymes that add a mark
• Readers: proteins that bind to and "interpret" the mark
• Erasers: enzymes that remove a mark

Histone Modifiers

• Do not bind to DNA themselves
  • can be recruited by:
    • Histone modification
    • Transcription factors
    • RNA
    • DNA damage
• Act as transcriptional co-regulators
• Enhance activities of transcriptional repressors or activators

General Roles of Histone Modifications

• Intrinsic
• Extrinsic
• Effector-mediated

Techniques to Study Histone Modifications

• Chromatin immunoprecipitation (ChIP): Strategy for localization histone marks 
• Mass Spectrometry: requires digestion of histones

Roles of Acetylation(乙酰化)

Roles of Lysine(赖氨酸) Methylation

Co-occurrence of activating and repressive lysine methylation

Position of histone modifications

Lysine Demethylation(脱甲基化)

Overview of ChIP-Seq analysis

ENCODE: Study nine marks in nine human cell lines

ChromHMM: Chromatin state discovery and characterization

Super-enhancers (multiple myeloma(骨髓瘤) as a case study)

Epigenetic alterations in cancer (Histone modifications)

这一章好多都看不懂。。。