Abstract 940: Global Analysis of Histone Modifications and Long-range Chromatin Interactions Revealed the Differential Cistrome Changes and Novel Transcriptional Players in Dilated Cardiomyopathy

AbstractThe human genome is partitioned into a collection of genomic features, inclusive of genes, transposable elements, lamina interacting regions, early replicating control elements and cis-regulatory elements, such as promoters, enhancers, and anchors of chromatin interactions. Uneven distribution of these features within chromosomes gives rise to clusters, such as topologically associating domains (TADs), lamina-associated domains, clusters of cis-regulatory elements or large organized chromatin lysine (K) domains (LOCKs). Here we show that LOCKs from diverse histone modifications discriminate primitive from differentiated cell types. Active LOCKs (H3K4me1, H3K4me3 and H3K27ac) cover a higher fraction of the genome in primitive compared to differentiated cell types while repressive LOCKs (H3K9me3, H3K27me3 and H3K36me3) do not. Active LOCKs in differentiated cells lie proximal to highly expressed genes while active LOCKs in primitive cells tend to be bivalent. Genes proximal to bivalent LOCKs are minimally expressed in primitive cells. Furthermore, bivalent LOCKs populate TAD boundaries and are preferentially bound by regulators of chromatin interactions, including CTCF, RAD21 and ZNF143. Together, our results argue that LOCKs discriminate primitive from differentiated cell populations.

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HiChIP and Hi-C Protocol Optimized for Primary Murine T Cells

Methods and Protocols ◽

10.3390/mps4030049 ◽

2021 ◽

Vol 4 (3) ◽

pp. 49

Author(s):

Tomas Zelenka ◽

Charalampos Spilianakis

Keyword(s):

T Cells ◽

Long Range ◽

Three Dimensional ◽

Cell Types ◽

Range Interaction ◽

Chromatin Interactions ◽

Optimized Protocol ◽

Long Range Interaction ◽

Chromatin Compactness ◽

Detailed Protocol

The functional implications of the three-dimensional genome organization are becoming increasingly recognized. The Hi-C and HiChIP research approaches belong among the most popular choices for probing long-range chromatin interactions. A few methodical protocols have been published so far, yet their reproducibility and efficiency may vary. Most importantly, the high frequency of the dangling ends may dramatically affect the number of usable reads mapped to valid interaction pairs. Additionally, more obstacles arise from the chromatin compactness of certain investigated cell types, such as primary T cells, which due to their small and compact nuclei, impede limitations for their use in various genomic approaches. Here we systematically optimized all the major steps of the HiChIP protocol in T cells. As a result, we reduced the number of dangling ends to nearly zero and increased the proportion of long-range interaction pairs. Moreover, using three different mouse genotypes and multiple biological replicates, we demonstrated the high reproducibility of the optimized protocol. Although our primary goal was to optimize HiChIP, we also successfully applied the optimized steps to Hi-C, given their significant protocol overlap. Overall, we describe the rationale behind every optimization step, followed by a detailed protocol for both HiChIP and Hi-C experiments.

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Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus

Cell Research ◽

10.1038/cr.2014.35 ◽

2014 ◽

Vol 24 (5) ◽

pp. 513-531 ◽

Cited By ~ 343

Author(s):

Jian-Feng Xiang ◽

Qing-Fei Yin ◽

Tian Chen ◽

Yang Zhang ◽

Xiao-Ou Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Long Range ◽

Human Colorectal Cancer ◽

Chromatin Interactions

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Human PRE-PIK3C2B exhibits long-range intra- and inter-chromosomal interactions with genomic regions enriched in repressive marks

10.1101/2020.11.11.378745 ◽

2020 ◽

Author(s):

Jayant Maini ◽

Ankit Kumar Pathak ◽

Kausik Bhattacharyya ◽

Narendra Kumar ◽

Ankita Narang ◽

...

Keyword(s):

Long Range ◽

Meta Analysis ◽

Range Interaction ◽

Dual Nature ◽

Polycomb Response Element ◽

Chromatin Interactions ◽

Long Range Interaction ◽

Intergenic Regions ◽

Genomic Regions ◽

Transcriptional Start Sites

AbstractHuman PRE-PIK3C2B is a dual nature polycomb response element that interacts with both polycomb as well as trithorax members. In the current study, using 4C-Seq (Capturing Circular Chromosomal Conformation-Sequencing), we identified long-range chromatin interactions associated with PRE-PIK3C2B and validated them with 3C-PCR. We identified both intra-as well as inter-chromosomal interactions, a large proportion of which were found to be closely distributed around transcriptional start sites (TSS). A significant number of interactions were also found to be associated with heterochromatic regions. Meta-analysis of ENCODE ChIP-Seq data identified an overall enrichment of YY1, CTCF as well as histone modification such as H3K4me3 and H3K27me marks in different cell lines. Almost 90% interactions were derived from either intronic or intergenic regions. among which large proportions of intronic interactors were either unique sequences or LINE/SINE derived. In case of intergenic interactions, majority of the interaction were associated with LINE/SINE repeats. We further found that genes proximal to the interactor sequences were co-expressed, they showed reduced expression. To the best of our knowledge this is one of the early demonstrations of long-range interaction of PRE sequences in human genome.

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