3 results
63438 Differential chromatin accessibility at dorsal root ganglia enhancers is associated with nerve injury
- Kimberly E. Stephens, Weiqiang Zhou, Zhicheng Ji, Hongkai Ji, Yun Guan, Sean D. Taverna
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, p. 5
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ABSTRACT IMPACT: Our improved understanding of the changes in chromatin accessibility that occur in persistent pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG. OBJECTIVES/GOALS: Efforts to understand genetic variability involved in an individual’s susceptibility to persistent pain support a role for upstream regulation by epigenetic mechanisms. Our objective was to examine the transcriptomic and epigenetic basis of persistent pain following nerve injury. METHODS/STUDY POPULATION: We used a multiomic approach to identify novel molecular pathways associated with nerve injury-induced pain hypersensitivity. Adult Sprague Dawley rats were randomized to Chronic Constriction Injury (CCI) to the sciatic nerve or no treatment (naive). The ipsilateral L4-L6 dorsal root ganglia (DRG)s were removed on Day 14 and used for ChIP-seq for H3K4me1, ATAC-seq, and RNA-seq. We assessed for differential chromatin accessibility, transcription factor motifs, and enrichment for biological processes in chromatin accessible regions associated with cis-regulatory regions identified by ATAC-seq and H3K4me1 enrichment. Luciferase assays determined the functional significance of these sequences. RESULTS/ANTICIPATED RESULTS: We identified 58,446 genomic regions where H3K4me1 enrichment overlapped with chromatin accessibility. Differential analysis identified 2145 of these 58,446 regions that had changes in accessibility after CCI. The majority of these regions were located in introns or intergenic regions. Functional annotation of the differentially accessible regions identified disparate molecular functions enriched following nerve injury which suggests that altered chromatin structure plays a role in the development of mechanical hypersensitivity. Motif analysis identified specific transcription factor families whose binding sequences were enriched in regions of increased or decreased accessibility. Luciferase assays showed significant enhancement or repression of gene transcription. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our data provides a comprehensive map of chromatin accessibility changes in the DRG after CCI and emphasizes the importance of chromatin structure in the development and maintenance of chronic pain.
Maternal postpartum plasma folate status and preterm birth in a high-risk US population
- Bolanle Olapeju, Ahmed Saifuddin, Guoying Wang, Yuelong Ji, Xiumei Hong, Ramkripa Raghavan, Amber Summers, Amaris Keiser, Hongkai Ji, Barry Zuckerman, Christina Yarrington, Lingxin Hao, Pamela J Surkan, Tina L Cheng, Xiaobin Wang
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- Journal:
- Public Health Nutrition / Volume 22 / Issue 7 / May 2019
- Published online by Cambridge University Press:
- 29 November 2018, pp. 1281-1291
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Objective
While maternal folate deficiency has been linked to poor pregnancy outcomes such as neural tube defects, anaemia and low birth weight, the relationship between folate and preterm birth (PTB) in the context of the US post-folic acid fortification era is inconclusive. We sought to explore the relationship between maternal folate status and PTB and its subtypes, i.e. spontaneous and medically indicated PTB.
DesignObservational study.
SettingBoston Birth Cohort, a predominantly urban, low-income, race/ethnic minority population at a high risk for PTB.
ParticipantsMother–infant dyads (n 7675) enrolled in the Boston Birth Cohort. A sub-sample (n 2313) of these dyads had maternal plasma folate samples collected 24–72 h after delivery.
ResultsUnadjusted and adjusted logistic regressions revealed an inverse relationship between the frequency of multivitamin supplement intake and PTB. Compared with less frequent use, multivitamin supplement intake 3–5 times/week (adjusted OR (aOR) = 0·78; 95 % CI 0·64, 0·96) or >5 times/week (aOR = 0·77; 95 % CI 0·64, 0·93) throughout pregnancy was associated with reduced risk of PTB. Consistently, higher plasma folate levels (highest v. lowest quartile) were associated with lower risk of PTB (aOR = 0·74; 95 % CI 0·56, 0·97). The above associations were similar among spontaneous and medically indicated PTB.
ConclusionsIf confirmed by future studies, our findings raise the possibility that optimizing maternal folate levels across pregnancy may help to reduce the risk of PTB among the most vulnerable US population in the post-folic acid fortification era.
5 - Integrative Analysis of Multiple ChIP-X Data Sets Using Correlation Motifs
- from Part A - Horizontal Meta-Analysis
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- By Hongkai Ji, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, Yingying Wei, The Chinese University of Hong Kong, Hong Kong
- George Tseng, University of Pittsburgh, Debashis Ghosh, Pennsylvania State University, Xianghong Jasmine Zhou, University of Southern California
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- Book:
- Integrating Omics Data
- Published online:
- 05 September 2015
- Print publication:
- 23 September 2015, pp 110-132
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Summary
Abstract
Genome-wide chromatin immunoprecipitation experiments including ChIP-seq and ChIP-chip, jointly referred to as ChIP-X, are high-throughput technologies to map protein-DNA interactions in the genome. When multiple related ChIP-X data sets are available, separately analyzing each data set is not optimal because it may lack power to detect consistent but relatively weak signals in multiple studies. Jointly analyzing all data sets may allow one to borrow information across studies to improve signal detection. However, a common problem in data integration is the difficulty in handling data set–specific signals that cannot be dealt with by simply assuming that the signal status for each genomic locus is the same across all studies. An integration model that naively enumerates all possible study specificity patterns, conversely, has exponential complexity because there are 2D possible combinatorial signal presence and absence patterns for D studies. Correlation motifs provide a useful solution to this problem. By introducing a small number of latent probability vectors called correlation motifs, this approach can describe the major correlation structure among multiple data sets, which can then be used to guide information sharing across data sets. The correlation motif approach is capable of improving signal detection. At the same time, it does not have the problem of exponential model complexity and is flexible enough to handle all possible data set–specific signal configurations.
Introduction
Chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-seq) (Johnson et al., 2007; Barski et al., 2007) and ChIP coupled with genome tiling array hybridization (ChIP-chip) (Ren et al., 2000; Cawley et al., 2004) are two high-throughput technologies capable of mapping protein-DNA interactions (PDIs) genome-wide. These two technologies, collectively referred to as “ChIP-X,” have been widely used to produce information on transcription factor binding sites (TFBSs) (Johnson et al., 2007; Robertson et al., 2007), histone modifications (HMs) (Barski et al., 2007; Mikkelsen et al., 2007), nucleosome positioning (Schmid and Bucher, 2007), allele-specific PDIs (Mikkelsen et al., 2007; Rozowsky et al., 2011), variations of PDIs among the population (McDaniell et al., 2010; Kasowski et al., 2010), and the evolution of gene regulation (Schmidt et al., 2010). Today, ChIP-X has become an indispensable tool used by both individual investigators and large consortium projects such as the Encyclopedia of DNA Elements (ENCODE), modENCODE, and Roadmap Epigenomics consortia to annotate the human genome and epigenome (Consortium, 2012; Celniker et al., 2009; Bernstein et al., 2010).