Abstract

Histone H2B monoubiquitination is a key histone modification that has significant effects on chromatin higher-order structure and gene transcription. Multiple biological processes have been suggested to be tightly related to the dynamics of H2B monoubiquitination. However, a comprehensive understanding of biological roles of H2B monoubiquitination is still poorly understood. In the present study, we developed an efficient tool to disrupt endogenous H2B monoubiquitination levels by using an H2BK120R mutant construct expressed in human cells. Genome-wide microarray analysis of these cells revealed a potential global view of biological functions of H2B monoubiquitination. Bioinformatics analysis of our data demonstrated that while H2B monoubiquitination expectedly affected a number of previously reported biological pathways, we also uncovered the influence of this histone modification on many novel biological processes. Therefore, our work provided valuable information for understanding the role of H2B monoubiquitination and indicated potential directions for its further studies.

Highlights

  • The precise formation of chromatin by DNA and histones is essential for almost all types of biological phenomena including cell proliferation, differentiation, and migration

  • H2B monoubiquitination is a key histone modification that plays a significant role in various biological processes including stem cell differentiation, DNA damage response, and chromatin organization

  • Using this direct interference method, we revealed that overexpression of the H2BK120R mutant construct in human cell lines efficiently suppresses endogenous H2B monoubiquitination levels (Fig 1)

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Summary

Introduction

The precise formation of chromatin by DNA and histones is essential for almost all types of biological phenomena including cell proliferation, differentiation, and migration. A nucleosome is a repeating unit of chromatin that contains approximately 147 base pairs of DNA and core histones (H3, H4, H2A, and H2B). DNA is wrapped around octamers formed by these core histones [1,2,3,4]. It has been well established that histones can be modified by distinct and specific enzymes causing various modifications.

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