Advances in higher-order chromatin architecture: the move towards 4D genome

Abstract

In eukaryotes, the genome is hierarchically packed inside the nucleus, which facilitates physical contact between cis-regulatory elements (CREs), such as enhancers and promoters. Accumulating evidence highlights the critical role of higherorder chromatin structure in precise regulation of spatiotemporal gene expression under diverse biological contexts including lineage commitment and cell activation by external stimulus. Genomics and imaging-based technologies, such as Hi-C and DNA fluorescence in situ hybridization (FISH), have revealed the key principles of genome folding, while newly developed tools focus on improvement in resolution, throughput and modality at single-cell and population levels, and challenge the knowledge obtained through conventional approaches. In this review, we discuss recent advances in our understanding of principles of higher-order chromosome conformation and technologies to investigate 4D chromatin interactions. [BMB Reports 2021; 54(5): 233-245]

The era of 3D and spatial genomics

“…We briefly revisit the key methodologies that are at the heart of 3D genomicswhich enable 3D genome organization to be studied within cell populations and single cellsand then focus on emerging technologies that are igniting the field of spatial genomicsallowing the variation of (3D) genome organization to be studied across multicellular tissues. For more detailed side-by-side comparisons of the methods that have advanced the field of 3D genomics we refer to several excellent recent reviews [6][7][8][9][10][11]. We also do not discuss multiregion sequencing approaches that have been widely deployed to study genome variation with spatial resolution in tumors.…”

“…For a comprehensive overview of the possibilities and limitations of these and other 3C-derived methods and ligation-free alternatives, and summaries of how they have contributed to enrich our knowledge of the 3D genome, we refer to excellent recent reviews [7,[9][10][11].…”

“…Numerous approaches combining live-cell imaging and genome editing have been developed to study the temporal dynamics of chromatin architecture in living cells [87][88][89][90][91][92][93][94][95]. Owing to space constraints, we do not discuss these methods here and instead refer the readers to several reviews that have recently covered the subject [7,8,11,80,96].…”

Epigenetic nature of Arabidopsis thaliana telomeres

“…The basic units of chromatin are the nucleosomes, which consist of 146 bp of DNA wrapped around a histone octamer containing two dimers of histones H2A–H2B and a tetramer of histones H3 and H4 ( Luger et al, 1997 ). These basic chromatin units fold into more complex organizations that ultimately contribute to compact DNA and regulate its metabolism ( Jung and Kim, 2021 ). Two main kinds of chromatin organizations are found within the nucleus of eukaryotic cells: euchromatin and heterochromatin.…”

MINE is a method for detecting spatial density of regulatory chromatin interactions based on a MultI-modal NEtwork

“…Among the numerous physical mechanisms of chromatin formation, one type of model (Brackley et al, 2016;Di Pierro et al, 2016;Di Stefano et al, 2016;Fiorillo et al, 2020) considers the formation of chromatin structures mediated by chromatin interactions with molecular factors, such as architectural proteins, histone marks and non-coding RNAs (Jung and Kim, 2021). Specifically, the Strings and Binders Switch (SBS) model proposes that chromatin is a 'self-avoiding polymer' 5 / 25 surrounded by diffusive molecular factors (e.g., transcription factors) that anchor to cognate recognition sites on the chromosome to drive the chromatin folding process.…”