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Genome-wide binding analysis of 195 DNA binding proteins reveals “reservoir” promoters and human specific SVA-repeat family regulation

A key aspect in defining cell state is the complex choreography of DNA binding events in a given cell type, which in turn establishes a cell-specific gene-expression program. Here we wanted to take a deep analysis of DNA binding events and transcriptional output of a single cell state (K562 cells)....

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Autores principales: Smallegan, Michael J., Shehata, Soraya, Spradlin, Savannah F., Swearingen, Alison, Wheeler, Graycen, Das, Arpan, Corbet, Giulia, Nebenfuehr, Benjamin, Ahrens, Daniel, Tauber, Devin, Lennon, Shelby, Choi, Kevin, Huynh, Thao, Wieser, Tom, Schneider, Kristen, Bradshaw, Michael, Basken, Joel, Lai, Maria, Read, Timothy, Hynes-Grace, Matt, Timmons, Dan, Demasi, Jon, Rinn, John L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224974/
https://www.ncbi.nlm.nih.gov/pubmed/34166368
http://dx.doi.org/10.1371/journal.pone.0237055
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author Smallegan, Michael J.
Shehata, Soraya
Spradlin, Savannah F.
Swearingen, Alison
Wheeler, Graycen
Das, Arpan
Corbet, Giulia
Nebenfuehr, Benjamin
Ahrens, Daniel
Tauber, Devin
Lennon, Shelby
Choi, Kevin
Huynh, Thao
Wieser, Tom
Schneider, Kristen
Bradshaw, Michael
Basken, Joel
Lai, Maria
Read, Timothy
Hynes-Grace, Matt
Timmons, Dan
Demasi, Jon
Rinn, John L.
author_facet Smallegan, Michael J.
Shehata, Soraya
Spradlin, Savannah F.
Swearingen, Alison
Wheeler, Graycen
Das, Arpan
Corbet, Giulia
Nebenfuehr, Benjamin
Ahrens, Daniel
Tauber, Devin
Lennon, Shelby
Choi, Kevin
Huynh, Thao
Wieser, Tom
Schneider, Kristen
Bradshaw, Michael
Basken, Joel
Lai, Maria
Read, Timothy
Hynes-Grace, Matt
Timmons, Dan
Demasi, Jon
Rinn, John L.
author_sort Smallegan, Michael J.
collection PubMed
description A key aspect in defining cell state is the complex choreography of DNA binding events in a given cell type, which in turn establishes a cell-specific gene-expression program. Here we wanted to take a deep analysis of DNA binding events and transcriptional output of a single cell state (K562 cells). To this end we re-analyzed 195 DNA binding proteins contained in ENCODE data. We used standardized analysis pipelines, containerization, and literate programming with R Markdown for reproducibility and rigor. Our approach validated many findings from previous independent studies, underscoring the importance of ENCODE’s goals in providing these reproducible data resources. We also had several new findings including: (i) 1,362 promoters, which we refer to as ‘reservoirs,’ that are defined by having up to 111 different DNA binding-proteins localized on one promoter, yet do not have any expression of steady-state RNA (ii) Reservoirs do not overlap super-enhancer annotations and distinct have distinct properties from super-enhancers. (iii) The human specific SVA repeat element may have been co-opted for enhancer regulation and is highly transcribed in PRO-seq and RNA-seq. Collectively, this study performed by the students of a CU Boulder computational biology class (BCHM 5631 –Spring 2020) demonstrates the value of reproducible findings and how resources like ENCODE that prioritize data standards can foster new findings with existing data in a didactic environment.
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spelling pubmed-82249742021-07-19 Genome-wide binding analysis of 195 DNA binding proteins reveals “reservoir” promoters and human specific SVA-repeat family regulation Smallegan, Michael J. Shehata, Soraya Spradlin, Savannah F. Swearingen, Alison Wheeler, Graycen Das, Arpan Corbet, Giulia Nebenfuehr, Benjamin Ahrens, Daniel Tauber, Devin Lennon, Shelby Choi, Kevin Huynh, Thao Wieser, Tom Schneider, Kristen Bradshaw, Michael Basken, Joel Lai, Maria Read, Timothy Hynes-Grace, Matt Timmons, Dan Demasi, Jon Rinn, John L. PLoS One Research Article A key aspect in defining cell state is the complex choreography of DNA binding events in a given cell type, which in turn establishes a cell-specific gene-expression program. Here we wanted to take a deep analysis of DNA binding events and transcriptional output of a single cell state (K562 cells). To this end we re-analyzed 195 DNA binding proteins contained in ENCODE data. We used standardized analysis pipelines, containerization, and literate programming with R Markdown for reproducibility and rigor. Our approach validated many findings from previous independent studies, underscoring the importance of ENCODE’s goals in providing these reproducible data resources. We also had several new findings including: (i) 1,362 promoters, which we refer to as ‘reservoirs,’ that are defined by having up to 111 different DNA binding-proteins localized on one promoter, yet do not have any expression of steady-state RNA (ii) Reservoirs do not overlap super-enhancer annotations and distinct have distinct properties from super-enhancers. (iii) The human specific SVA repeat element may have been co-opted for enhancer regulation and is highly transcribed in PRO-seq and RNA-seq. Collectively, this study performed by the students of a CU Boulder computational biology class (BCHM 5631 –Spring 2020) demonstrates the value of reproducible findings and how resources like ENCODE that prioritize data standards can foster new findings with existing data in a didactic environment. Public Library of Science 2021-06-24 /pmc/articles/PMC8224974/ /pubmed/34166368 http://dx.doi.org/10.1371/journal.pone.0237055 Text en © 2021 Smallegan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Smallegan, Michael J.
Shehata, Soraya
Spradlin, Savannah F.
Swearingen, Alison
Wheeler, Graycen
Das, Arpan
Corbet, Giulia
Nebenfuehr, Benjamin
Ahrens, Daniel
Tauber, Devin
Lennon, Shelby
Choi, Kevin
Huynh, Thao
Wieser, Tom
Schneider, Kristen
Bradshaw, Michael
Basken, Joel
Lai, Maria
Read, Timothy
Hynes-Grace, Matt
Timmons, Dan
Demasi, Jon
Rinn, John L.
Genome-wide binding analysis of 195 DNA binding proteins reveals “reservoir” promoters and human specific SVA-repeat family regulation
title Genome-wide binding analysis of 195 DNA binding proteins reveals “reservoir” promoters and human specific SVA-repeat family regulation
title_full Genome-wide binding analysis of 195 DNA binding proteins reveals “reservoir” promoters and human specific SVA-repeat family regulation
title_fullStr Genome-wide binding analysis of 195 DNA binding proteins reveals “reservoir” promoters and human specific SVA-repeat family regulation
title_full_unstemmed Genome-wide binding analysis of 195 DNA binding proteins reveals “reservoir” promoters and human specific SVA-repeat family regulation
title_short Genome-wide binding analysis of 195 DNA binding proteins reveals “reservoir” promoters and human specific SVA-repeat family regulation
title_sort genome-wide binding analysis of 195 dna binding proteins reveals “reservoir” promoters and human specific sva-repeat family regulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224974/
https://www.ncbi.nlm.nih.gov/pubmed/34166368
http://dx.doi.org/10.1371/journal.pone.0237055
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