Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a potential regulator of H3K79me3

Muhammad Jbara; Noga Guttmann-Raviv; Suman Kumar Maity; Nabieh Ayoub; Ashraf Brik

doi:10.1016/j.bmc.2017.04.015

Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a potential regulator of H3K79me3

Muhammad Jbara, Noga Guttmann-Raviv, Suman Kumar Maity, Nabieh Ayoub, Ashraf Brik

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9. Herein we applied convergent total chemical protein synthesis to prepare trimethylated H3 at Lys79 to perform initial studies related to the regulation of this mark. Our study enabled us to identify KDM4D lysine demethylase as a potential regulator for trimethylated H3 at Lys79.

Original language	English
Pages (from-to)	4966-4970
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	25
Issue number	18
DOIs	https://doi.org/10.1016/j.bmc.2017.04.015
State	Published - 1 Jan 2017
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmc.2017.04.015

Cite this

@article{f1f75c27a96a43f09f69bb1b623c1126,

title = "Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a potential regulator of H3K79me3",

abstract = "Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9. Herein we applied convergent total chemical protein synthesis to prepare trimethylated H3 at Lys79 to perform initial studies related to the regulation of this mark. Our study enabled us to identify KDM4D lysine demethylase as a potential regulator for trimethylated H3 at Lys79.",

author = "Muhammad Jbara and Noga Guttmann-Raviv and Maity, {Suman Kumar} and Nabieh Ayoub and Ashraf Brik",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

month = jan,

day = "1",

doi = "10.1016/j.bmc.2017.04.015",

language = "English",

volume = "25",

pages = "4966--4970",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "18",

}

TY - JOUR

T1 - Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a potential regulator of H3K79me3

AU - Jbara, Muhammad

AU - Guttmann-Raviv, Noga

AU - Maity, Suman Kumar

AU - Ayoub, Nabieh

AU - Brik, Ashraf

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9. Herein we applied convergent total chemical protein synthesis to prepare trimethylated H3 at Lys79 to perform initial studies related to the regulation of this mark. Our study enabled us to identify KDM4D lysine demethylase as a potential regulator for trimethylated H3 at Lys79.

AB - Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9. Herein we applied convergent total chemical protein synthesis to prepare trimethylated H3 at Lys79 to perform initial studies related to the regulation of this mark. Our study enabled us to identify KDM4D lysine demethylase as a potential regulator for trimethylated H3 at Lys79.

UR - http://www.scopus.com/inward/record.url?scp=85018563586&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2017.04.015

DO - 10.1016/j.bmc.2017.04.015

M3 - Article

C2 - 28434780

AN - SCOPUS:85018563586

SN - 0968-0896

VL - 25

SP - 4966

EP - 4970

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 18

ER -

Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a potential regulator of H3K79me3

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this