Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation.

Abstract:

:Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. While significant progress has been made characterizing individual effector domains, the role of paired domains and how they function in a combinatorial fashion within chromatin are poorly defined. Here we show that the linked tandem Tudor and plant homeodomain (PHD) of UHRF1 (ubiquitin-like PHD and RING finger domain-containing protein 1) operates as a functional unit in cells, providing a defined combinatorial readout of a heterochromatin signature within a single histone H3 tail that is essential for UHRF1-directed epigenetic inheritance of DNA methylation. These findings provide critical support for the "histone code" hypothesis, demonstrating that multivalent histone engagement plays a key role in driving a fundamental downstream biological event in chromatin.

journal_name

Genes Dev

journal_title

Genes & development

authors

Rothbart SB,Dickson BM,Ong MS,Krajewski K,Houliston S,Kireev DB,Arrowsmith CH,Strahl BD

doi

10.1101/gad.220467.113

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

1288-98

issue

11

eissn

0890-9369

issn

1549-5477

pii

27/11/1288

journal_volume

27

pub_type

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