Association of ORCA/LRWD1 with repressive histone methyl transferases mediates heterochromatin organization

Nucleus
Sumanprava Giri, Supriya G Prasanth

Abstract

Heterochromatin mostly constitutes tightly packaged DNA, decorated with repressive histone marks, including histone H3 methylated at lysine 9, histone H4 methylated at lysine 20 and histone H3 methylated at lysine 27. Each of these marks is incorporated by specific histone lysine methyl transferases. While constitutive heterochromatin enriched with H3K9me3 and H4K20me3 occur within repetitive elements, including centromeres and telomeres, the facultative heterochromatin resides on the inactive X-chromosome and contains H3K27me3 mark. Origin recognition complex-associated (ORCA/LRWD1) protein is required for the initiation of DNA replication and also plays crucial roles in heterochromatin organization. ORCA associates with constitutive and facultative heterochromatin in human cells and binds to repressive histone marks. We demonstrate that ORCA binds to multiple repressive histone methyl transferases including G9a, GLP, Suv39h1 (H3K9me2/3), Suv420h1/h2 (H4K20me2/3) and EZH2 (H3K27me3). Removal of ORCA from human cells causes aberrations in the chromatin architecture. We propose that ORCA acts as a scaffold protein that enables the formation of multiple histone lysine methyltransferase complexes at heterochromatic sites thereby f...Continue Reading

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Citations

Sep 11, 2018·Nucleus·Varvara V PopovaDaria V Kopytova
Sep 23, 2018·Cells·Esperanza Hernández-CarraleroRaimundo Freire
Jun 10, 2017·Neurogenesis·Steven J DeimlingVincent Tropepe
Nov 17, 2020·Physiological Genomics·Adriana Z Corvalan, Hilary A Coller
Apr 30, 2021·Development·Jason M ScovellCarolina J Jorgez
May 21, 2021·Basic and Clinical Andrology·Jui-Hsiang HungYen-Ni Teng
Mar 12, 2020·Journal of Proteome Research·Victoria PhamMarie Classon

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Methods Mentioned

BETA
Pulldown
immunoprecipitation

Software Mentioned

ORCA

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