scholarly journals Lamina Associated Domains and Gene Regulation in Development and Cancer

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 271 ◽  
Author(s):  
Silke J.A. Lochs ◽  
Samy Kefalopoulou ◽  
Jop Kind
Keyword(s):  
Gene Regulation ◽  
Nuclear Lamina ◽  
Specific Gene ◽  
Chromatin Binding ◽  
Cell Type ◽  
Cell Type Specific ◽  
Dynamic Structures ◽  
Spatial Positioning ◽  
Genomic Regions

The nuclear lamina (NL) is a thin meshwork of filaments that lines the inner nuclear membrane, thereby providing a platform for chromatin binding and supporting genome organization. Genomic regions contacting the NL are lamina associated domains (LADs), which contain thousands of genes that are lowly transcribed, and enriched for repressive histone modifications. LADs are dynamic structures that shift spatial positioning in accordance with cell-type specific gene expression changes during differentiation and development. Furthermore, recent studies have linked the disruption of LADs and alterations in the epigenome with the onset of diseases such as cancer. Here we focus on the role of LADs and the NL in gene regulation during development and cancer.

scholarly journals FIREcaller: Detecting Frequently Interacting Regions from Hi-C Data

2019 ◽  
Author(s):  
Cheynna Crowley ◽  
Yuchen Yang ◽  
Yunjiang Qiu ◽  
Benxia Hu ◽  
Armen Abnousi ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Spatial Organization ◽  
R Package ◽  
Specific Gene ◽  
List Type ◽  
Cell Type ◽  
R Software ◽  
Computational Tools ◽  
Cell Type Specific ◽  
User Friendly

AbstractHi-C experiments have been widely adopted to study chromatin spatial organization, which plays an essential role in genome function. We have recently identified frequently interacting regions (FIREs) and found that they are closely associated with cell-type-specific gene regulation. However, computational tools for detecting FIREs from Hi-C data are still lacking. In this work, we present FIREcaller, a stand-alone, user-friendly R package for detecting FIREs from Hi-C data. FIREcaller takes raw Hi-C contact matrices as input, performs within-sample and cross-sample normalization, and outputs continuous FIRE scores, dichotomous FIREs, and super-FIREs. Applying FIREcaller to Hi-C data from various human tissues, we demonstrate that FIREs and super-FIREs identified, in a tissue-specific manner, are closely related to gene regulation, are enriched for enhancer-promoter (E-P) interactions, tend to overlap with regions exhibiting epigenomic signatures of cis-regulatory roles, and aid the interpretation or GWAS variants. The FIREcaller package is implemented in R and freely available at https://yunliweb.its.unc.edu/FIREcaller.Highlights– Frequently Interacting Regions (FIREs) can be used to identify tissue and cell-type-specific cis-regulatory regions.– An R software, FIREcaller, has been developed to identify FIREs and clustered FIREs into super-FIREs.

scholarly journals H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Andrey Poleshko ◽  
Cheryl L Smith ◽  
Son C Nguyen ◽  
Priya Sivaramakrishnan ◽  
Karen G Wong ◽  
...  
Keyword(s):  
Cell Division ◽  
Spatial Organization ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Positional Information ◽  
Specific Gene ◽  
Cell Type ◽  
Histone 3 ◽  
Spatial Positioning ◽  
Peripheral Heterochromatin

Cell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the parent. Lamina-associated domains (LADs) are regions of repressive heterochromatin positioned at the nuclear periphery that vary by cell type and contribute to cell-specific gene expression and identity. Here we show that histone 3 lysine 9 dimethylation (H3K9me2) is an evolutionarily conserved, specific mark of nuclear peripheral heterochromatin and that it is retained through mitosis. During mitosis, phosphorylation of histone 3 serine 10 temporarily shields the H3K9me2 mark allowing for dissociation of chromatin from the nuclear lamina. Using high-resolution 3D immuno-oligoFISH, we demonstrate that H3K9me2-enriched genomic regions, which are positioned at the nuclear lamina in interphase cells prior to mitosis, re-associate with the forming nuclear lamina before mitotic exit. The H3K9me2 modification of peripheral heterochromatin ensures that positional information is safeguarded through cell division such that individual LADs are re-established at the nuclear periphery in daughter nuclei. Thus, H3K9me2 acts as a 3D architectural mitotic guidepost. Our data establish a mechanism for epigenetic memory and inheritance of spatial organization of the genome.

scholarly journals Global Mapping of H3K4me1 and H3K4me3 Reveals the Chromatin State-Based Cell Type-Specific Gene Regulation in Human Treg Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27770 ◽  
Author(s):  
Yi Tian ◽  
Zhengcai Jia ◽  
Jun Wang ◽  
Zemin Huang ◽  
Jun Tang ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Treg Cells ◽  
Chromatin State ◽  
Specific Gene ◽  
Cell Type ◽  
Global Mapping ◽  
Cell Type Specific

scholarly journals H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis

2019 ◽  
Author(s):  
Andrey Poleshko ◽  
Cheryl L. Smith ◽  
Son C. Nguyen ◽  
Priya Sivaramakrishnan ◽  
John Isaac Murray ◽  
...  
Keyword(s):  
Cell Division ◽  
Spatial Organization ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Positional Information ◽  
Specific Gene ◽  
Cell Type ◽  
Histone 3 ◽  
Spatial Positioning ◽  
Peripheral Heterochromatin

AbstractCell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the parent. Lamina-associated domains (LADs) are regions of repressive heterochromatin positioned at the nuclear periphery that vary by cell type and contribute to cell-specific gene expression and identity. Here we show that histone 3 lysine 9 dimethylation (H3K9me2) is an evolutionarily conserved, specific mark of nuclear peripheral heterochromatin and that it is retained through mitosis. During mitosis, phosphorylation of histone 3 serine 10 temporarily shields the H3K9me2 mark allowing for dissociation of chromatin from the nuclear lamina. Using high-resolution 3D immuno-oligoFISH, we demonstrate that H3K9me2-enriched genomic regions, which are positioned at the nuclear lamina in interphase cells prior to mitosis, re-associate with the forming nuclear lamina before mitotic exit. The H3K9me2 modification of peripheral heterochromatin ensures that positional information is safeguarded through cell division such that individual LADs are re-established at the nuclear periphery in daughter nuclei. Thus, H3K9me2 acts as a 3D architectural mitotic guidepost. Our data establish a mechanism for epigenetic memory and inheritance of spatial organization of the genome.

Identification of the mouse neurochondrin promoter region and the responsible region for cell type specific gene regulation

2004 ◽  
Vol 356 (2) ◽  
pp. 107-110 ◽  
Author(s):  
Minori Dateki ◽  
Reiko Mochizuki ◽  
Kazuyuki Yanai ◽  
Akiyoshi Fukamizu
Keyword(s):  
Gene Regulation ◽  
Promoter Region ◽  
Specific Gene ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals A new class of constitutively active super-enhancers is associated with fast recovery of 3D chromatin loops

2018 ◽  
Author(s):  
Jayoung Ryu ◽  
Hyunwoong Kim ◽  
Dongchan Yang ◽  
Andrew J. Lee ◽  
Inkyung Jung
Keyword(s):  
Gene Regulation ◽  
Comprehensive Analysis ◽  
Specific Gene ◽  
Cell Type ◽  
Chromatin Loops ◽  
New Class ◽  
Genome Regulation ◽  
Super Enhancer ◽  
Cell Tissue ◽  
Cell Type Specific

AbstractSuper-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation. However, little is known about the function of super-enhancers beyond gene regulation. In this study, through a comprehensive analysis of super-enhancers in 30 human cell/tissue types, we identified a new class of super-enhancers which are constitutively active across most cell/tissue types. These ‘common’ super-enhancers are associated with universally highly expressed genes in contrast to the canonical definition of super-enhancers that assert cell-type specific gene regulation. In addition, the genome sequence of these super-enhancers is highly conserved by evolution and among humans, advocating their universal function in genome regulation. Integrative analysis of 3D chromatin loops demonstrates that, in comparison to the cell-type specific super-enhancers, the cell-type common super-enhancers present a striking association with rapidly recovering loops. We propose that a new class of super-enhancers may play an important role in the early establishment of 3D chromatin structure.BackgroundSuper-enhancers or stretch enhancers are defined by a strong enrichment of mediators and transcription-regulating proteins, appearing to play a deterministic role in cellular identity by controlling the expression of cell-type specific genes[1, 2]. Previous studies have revealed the critical function of super-enhancers during development and differentiation[3]. The enrichment of disease-associated single nucleotide polymorphism (SNP) in super-enhancers compared to that of typical enhancers proposed a substantial link between super-enhancers and many complex human diseases[2]. In addition, a set of recent studies have proposed potential functions of super-enhancers in the extremely long-range chromatin communications and the establishment of 3D chromatin loops[4]. These results suggest a more universal role of super-enhancers in genome regulation apart from cell-type specific gene regulation, but little is known about the mechanisms underlying these various functions. To extend the current knowledge of super-enhancers and their biological roles, we conducted a comprehensive analysis of super-enhancer activities across 30 human cell/tissue types. Our analysis suggests that a substantial number of super-enhancers exhibits prevalent activities across cell-types in terms of H3K27ac signals, and that these non-canonical super-enhancers are involved in the formation of fast recovering chromatin loops.NoteA genome browser session has been set up for visualization of the super-enhancer domains described in the current study– https://genome.ucsc.edu/cgi-bin/hgTracks?hgS-doOtherUser=submit&hgS-otherUserName=abundantiavosliberabit&hgS-otherUserSessionName=SuperEnhancerDomain

Sign in / Sign up

Export Citation Format

Share Document