Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome

Fang, Qianglin; Chen, Ping; Wang, Mingzhu; Fang, Junshun; Yang, Na; Li, Guohong; Xu, Rui-Ming

doi:10.7554/elife.11911

Cited by 37 publications

(47 citation statements)

References 37 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IE1 exhibits two physically separable histone interacting regions with differential binding specificities for H2A-H2B dimers and H3-H4 dimers or tetramers. The H2A-H2B binding region was mapped to an evolutionarily conserved nucleosome binding motif (amino acids 479-488) within the chromatin tethering domain (CTD) at the C-terminus [229,230]. This motif docks with the acidic patch formed by H2A-H2B on the nucleosome surface [229,230].…”

Section: Role In Chromatin-based Epigenetic Regulationmentioning

confidence: 99%

“…The H2A-H2B binding region was mapped to an evolutionarily conserved nucleosome binding motif (amino acids 479-488) within the chromatin tethering domain (CTD) at the C-terminus [229,230]. This motif docks with the acidic patch formed by H2A-H2B on the nucleosome surface [229,230]. The consequences of the IE1-nucleosome interaction have not been fully elucidated, but they appear to include alterations to higher order chromatin structure [230].…”

Section: Role In Chromatin-based Epigenetic Regulationmentioning

confidence: 99%

See 1 more Smart Citation

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

Adamson

Nevels

2020

Viruses

View full text Add to dashboard Cite

The human cytomegalovirus (HCMV), one of eight human herpesviruses, establishes lifelong latent infections in most people worldwide. Primary or reactivated HCMV infections cause severe disease in immunosuppressed patients and congenital defects in children. There is no vaccine for HCMV, and the currently approved antivirals come with major limitations. Most approved HCMV antivirals target late molecular processes in the viral replication cycle including DNA replication and packaging. “Bright and early” events in HCMV infection have not been exploited for systemic prevention or treatment of disease. Initiation of HCMV replication depends on transcription from the viral major immediate-early (IE) gene. Alternative transcripts produced from this gene give rise to the IE1 and IE2 families of viral proteins, which localize to the host cell nucleus. The IE1 and IE2 proteins are believed to control all subsequent early and late events in HCMV replication, including reactivation from latency, in part by antagonizing intrinsic and innate immune responses. Here we provide an update on the regulation of major IE gene expression and the functions of IE1 and IE2 proteins. We will relate this insight to experimental approaches that target IE gene expression or protein function via molecular gene silencing and editing or small chemical inhibitors.

show abstract

Section: Role In Chromatin-based Epigenetic Regulationmentioning

confidence: 99%

Section: Role In Chromatin-based Epigenetic Regulationmentioning

confidence: 99%

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

Adamson

Nevels

2020

Viruses

View full text Add to dashboard Cite

show abstract

“…Can Zika virus, a flavivirus, use unstructured proteins to tether host chromatin via the nuclesome surface, like other viral peptides such as the LANA peptide from Kaposi´s Sarcoma-associated Herpes virus [21] and Cytomegalovirus (CMV) [22]?…”

Section: Journal Ofmentioning

confidence: 99%

Brief Insights into Zika-Microcephaly Mechanism

Gm¹,

Itg²,

Aa³

2017

Clin Exp Pharmacol

View full text Add to dashboard Cite

After recent reports attesting a straight correlation between Zika infection and brain disorders in new-borns, research questions now focus on establishing causality and the mechanisms underlying it. Studies involving monolayer cultures, murine and human brain tissue slices and the cerebral organoid system have provided important information regarding neuronal damage, but the precise mechanisms underlying neuronal cell tropism and cell damage have not been elucidated. Herein, we discuss the possibility that Zika virus proteins enter the nucleus by a brief search for nuclear signal localization and for potential nucleosome binding motifs using a bioinformatics approach and point to other questions that should be the focus of research aiming to understand Zika-virus associated cell-damage.

show abstract

“…If the H4 N‐tail is removed, nucleosomal arrays were found no longer to be condensed normally . Remarkably, the “acidic patch” was found to be a “common” binding site for several nonhistone proteins , i.e., LANA , IE1 , RCC1 , Sir3 , and PRC1 , many of which are thought to participate in the structure regulation of chromatin fiber .…”

Section: Introductionmentioning

confidence: 99%

Higher‐order structure of the 30‐nm chromatin fiber revealed by cryo‐EM

Zhu

2016

IUBMB Life

Self Cite

View full text Add to dashboard Cite

Genomic DNA is hierarchically packaged into chromatin in eukaryotes. As a central-level chromatin structure between nucleosomal arrays and higher order organizations, 30 nm chromatin fiber, and its dynamics play a crucial role in regulating DNA accessibility for gene transcription. However, despite extensive efforts over three decades, the higher-order structure of the 30 nm chromatin fiber remains unresolved and controversial. We have recently reconstituted the 30 nm chromatin fibers from 12 nucleosomal arrays in vitro in the presence of linker histone H1, and determined their cryo-EM structures at resolution of 11 Å (Song et al., Science 344,[376][377][378][379][380]. Here, we briefly reviewed the higher-order structure studies of chromatin fibers, mainly focusing on the insights from the cryo-EM structures we recently solved. V C 2016 IUBMB Life, 68(11): [873][874][875][876][877][878] 2016

show abstract

Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome

Cited by 37 publications

References 37 publications

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

Brief Insights into Zika-Microcephaly Mechanism

Higher‐order structure of the 30‐nm chromatin fiber revealed by cryo‐EM

Contact Info

Product

Resources

About