HDAC1 | histone deacetylases | 组蛋白脱乙酰基酶 | 关键调控因子

前篇:EZH2 | Ezh2 | 组蛋白甲基化酶/组蛋白甲基转移酶 | 关键调控因子 

类似Ezh2,都是比较火爆的核心调控因子,与多种疾病和通路有关,可以搜到很多文章都围绕它来讲故事。

 

目的:鉴定出HDAC1激活和抑制的靶基因。

老套路:

  • HDAC1上调,则其激活的target genes必然也会上调;既然是TF,那在promoter肯定有motif enrichment;
  • HDAC1上调,则其抑制的target genes必然也会下调;它是以复合体的形式存在的,可以衡量一下复合体的活性;

缺点:

  • 这么比也没错,但肯定不是最好的,需要wild-type and HDAC1-deficient cells的RNA-seq数据;

 

背景知识

Histone deacetylases (HDACs) catalyze the removal of acetyl groups from core histones.

组蛋白脱乙酰基酶(HDAC)催化从核心组蛋白中除去乙酰基。

 

Because of their capacity to induce local condensation of chromatin, HDACs are generally considered repressors of transcription.

由于HDAC具有诱导染色质局部浓缩的能力,因此通常认为HDAC是转录的阻遏物。

 

 

 

 

先了解HDAC的基本情况

在control里面的表达情况

在HSCR里的表达情况

再找targets

 

 

 

 

Sin3A, NuRD, and CoREST corepressor complexes

在表达文件里确定的subunits的基因名:

Sin3 complex:
- HDAC1
- HDAC2
- RBBP4 (RbAp46)
- RBBP7 (RbAp48)
- SAP30
- SAP18
- SUDS3 (SDS3)

NuRD complex:
- HDAC1
- HDAC2
- CHD3
- CHD4
- MBD2
- MBD3
- MTA1
- MTA2
- MTA3
- GATAD2A
- GATAD2B
- RBBP4 (RbAp46)
- RBBP7 (RbAp48)

CoREST complex:
- HDAC1
- HDAC2
- KDM1A (LSD1)
- PHF21A (BHC80)
- CTBP1 (CtBP)
- RCOR1
- RCOR2
- RCOR3

  

可以设计一个几何平均来衡量这几个complex的活性。

 

 

 

 

待续~

 

 

参考:

google image search: HDAC1

Google HDAC1 target:

Negative and Positive Regulation of Gene Expression by Mouse Histone Deacetylase 1 - 2006 - IF 3.735

The physiological roles of histone deacetylase (HDAC) 1 and 2: complex co-stars with multiple leading parts - 2013 - Biochem Soc Trans - IF 3

A Comparative Study of Target Engagement Assays for HDAC1 Inhibitor Profiling

Histone deacetylase (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells

Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation - 2010 - PNAS - HDAC1和HDAC2的区别

3 complexes:

Sin3 - Master Scaffold and Transcriptional Corepressor

NuRD: A multi-faceted chromatin remodeling complex in regulating cancer biology

 

posted @ 2021-03-17 20:46  Life·Intelligence  阅读(31)  评论(0编辑  收藏
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