Placenta and fetal brain share a neurodevelopmental disorder DNA methylation profile in a mouse model of prenatal PCB exposure

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SUMMARY

Polychlorinated biphenyls (PCBs) are developmental neurotoxicants implicated as environmental risk factors for neurodevelopmental disorders (NDDs). Here, we report the effects of prenatal exposure to a human-relevant mixture of PCBs on the DNA methylation profiles of mouse placenta and fetal brain. Thousands of differentially methylated regions (DMRs) distinguish placenta and fetal brain from PCB-exposed mice from sex-matched vehicle controls. In both placenta and fetal brain, PCB-associated DMRs are enriched for functions related to neurodevelopment and cellular signaling and enriched within regions of bivalent chromatin. The placenta and brain PCB DMRs overlap significantly and map to a shared subset of genes enriched for Wnt signaling, Slit/Robo signaling, and genes differentially expressed in NDD models. The consensus PCB DMRs also significantly overlap with DMRs from human NDD brain and placenta. These results demonstrate that PCB-exposed placenta contains a subset of DMRs that overlap fetal brain DMRs relevant to an NDD.

In brief

Exposure to polychlorinated biphenyls is a risk factor for a neurodevelopmental disorder. In a mouse model of exposure to a human-relevant mixture, Laufer et al. utilize WGBS to profile DNA methylation within placenta and fetal brain. Both tissues display shared alterations at regions related to neurodevelopment and autism spectrum disorders.

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The Sequence Alignment/Map format and SAMtools

Heng Li, Bob Handsaker, Alec Wysoker … (2009)

Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk

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STAR: ultrafast universal RNA-seq aligner.

Alexander Dobin, Carrie A. Davis, Felix Schlesinger … (2013)

Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.

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Fast gapped-read alignment with Bowtie 2.

Ben Langmead, Steven L Salzberg (2023)

As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.

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Author and article information

Journal

Journal ID (nlm-journal-id): 101573691

Journal ID (pubmed-jr-id): 39703

Journal ID (nlm-ta): Cell Rep

Journal ID (iso-abbrev): Cell Rep

Title: Cell reports

ISSN (Electronic): 2211-1247

Publication date Nihms-submitted: 16 March 2022

Publication date (Print): 01 March 2022

Publication date PMC-release: 23 March 2022

Volume: 38

Issue: 9

Page: 110442

Affiliations

[1 ]Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA

[2 ]UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USA

[3 ]MIND Institute, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA

[4 ]Perinatal Origins of Disparities Center, University of California, Davis, Davis, CA 95616, USA

[5 ]Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA

[6 ]Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, CA 95616, USA

[7 ]Present address: Department of OMNI Bioinformatics, Genentech, Inc., South San Francisco, CA 94080, USA

[8 ]These authors contributed equally

[9 ]Lead contact

Author notes

AUTHOR CONTRIBUTIONS

J.M.L., P.J.L., R.J.S., B.I.L., K.N., and A.E.V. designed the study. J.M.L., P.J.L., and R.J.S. acquired funding for the study. J.M.L. and P.J.L. supervised

the project. K.N., A.E.V., and D.H.Y. performed the mouse work. K.N. and B.I.L. performed the DNA and RNA isolations. B.I.L. and K.N. performed the bioinformatic analyses. B.I.L. interpreted the results and wrote the manuscript with intellectual contributions from J.M.L. J.M.L., P.J.L., and K.N. edited the manuscript. All authors reviewed and approved the final manuscript.

[* ]Correspondence: jmlasalle@ 123456ucdavis.edu

Article

Manuscript ID: NIHMS1785218

DOI: 10.1016/j.celrep.2022.110442

PMC ID: 8941983

PubMed ID: 35235788

SO-VID: b8fef11d-371e-4330-8639-72b7ca5ec998

License:

This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/).

Placenta and fetal brain share a neurodevelopmental disorder DNA methylation profile in a mouse model of prenatal PCB exposure

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GLUT4 biology

Most cited references 113

The Sequence Alignment/Map format and SAMtools

STAR: ultrafast universal RNA-seq aligner.

Fast gapped-read alignment with Bowtie 2.

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