CRL4DCAF8 Ubiquitin Ligase Targets Histone H3K79 and Promotes H3K9 Methylation in the Liver | Zendy

Gaofeng Li | Zendy; Tong Ji | Zendy; Chen Jiang | Zendy; Yufei Fu | Zendy; Lidan Hou | Zendy; Feng Yan | Zendy; Tingyue Zhang | Zendy; Tianyu Song | Zendy; Jie Zhao | Zendy; Yoko Endo | Zendy; Hui Lin | Zendy; Xiujun Cai | Zendy; Yong Cang | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

CRL4DCAF8 Ubiquitin Ligase Targets Histone H3K79 and Promotes H3K9 Methylation in the Liver

Author(s) -

Gaofeng Li,

Tong Ji,

Chen Jiang,

Yufei Fu,

Lidan Hou,

Feng Yan,

Tingyue Zhang,

Tianyu Song,

Jie Zhao,

Yoko Endo,

Hui Lin,

Xiujun Cai,

Yong Cang

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.01.039

Subject(s) - biology , ubiquitin ligase , ubiquitin , epigenetics , histone , dna methylation , microbiology and biotechnology , gene silencing , histone h3 , methylation , gene expression , gene , genetics

Transcription from chromosomes is regulated by posttranslational modifications to histones, such as methylation and ubiquitination. Monoubiquitination of histones H2A and H2B influences H3 methylation to reinforce the activation or repression of gene expression. Here, we provide evidence that H3 polyubiquitination represses transcription of fetal and cell-cycle genes in postnatal mouse liver by crosstalk with H3K9 methylation. We found that the CRL4 ubiquitin ligase targets H3 for polyubiquitination at K79 via the DCAF8 substrate receptor in hepatocytes. Genetic inactivation of DCAF8 and overexpression of an H3K79 mutant in cells or inducible deletion of CRL4 in mouse liver abrogates H3 ubiquitination, reactivates the expression of fetal liver and cell-cycle genes by interfering with methylated H3K9 occupancy, and leads to cell senescence. Restoring CRL4 DCAF8 expression in cells with decreased H3 ubiquitination reinstates the epigenetic gene silencing. Our results suggest that progressive H3 ubiquitination plays an important role in postnatal liver maturation.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research