A Chromatin Accessibility Atlas of the Developing Human Telencephalon. Markenscoff-Papadimitriou, E., Whalen, S., Przytycki, P., Thomas, R., Binyameen, F., Nowakowski, T. J, Kriegstein, A. R, Sanders, S. J, State, Matthew W, Pollard, K. S, & Rubenstein, J. L Cell, 182(3):754–769.e18, June, 2020. abstract bibtex To discover regulatory elements driving the specificity of gene expression in different cell types and regions of the developing human brain, we generated an atlas of open chromatin from nine dissected regions of the mid-gestation human telencephalon, as well as microdissected upper and deep layers of the prefrontal cortex. We identified a subset of open chromatin regions (OCRs), termed predicted regulatory elements (pREs), that are likely to function as developmental brain enhancers. pREs showed temporal, regional, and laminar differences in chromatin accessibility and were correlated with gene expression differences across regions and gestational ages. We identified two functional de novo variants in a pRE for autism risk gene SLC6A1, and using CRISPRa, demonstrated that this pRE regulates SCL6A1. Additionally, mouse transgenic experiments validated enhancer activity for pREs proximal to FEZF2 and BCL11A. Thus, this atlas serves as a resource for decoding neurodevelopmental gene regulation in health and disease.
@ARTICLE{Markenscoff-Papadimitriou2020-bc,
title = "A Chromatin Accessibility Atlas of the Developing Human
Telencephalon",
author = "Markenscoff-Papadimitriou, Eirene and Whalen, Sean and Przytycki,
Pawel and Thomas, Reuben and Binyameen, Fadya and Nowakowski,
Tomasz J and Kriegstein, Arnold R and Sanders, Stephan J and
{State, Matthew W} and Pollard, Katherine S and Rubenstein, John
L",
abstract = "To discover regulatory elements driving the specificity of gene
expression in different cell types and regions of the developing
human brain, we generated an atlas of open chromatin from nine
dissected regions of the mid-gestation human telencephalon, as
well as microdissected upper and deep layers of the prefrontal
cortex. We identified a subset of open chromatin regions (OCRs),
termed predicted regulatory elements (pREs), that are likely to
function as developmental brain enhancers. pREs showed temporal,
regional, and laminar differences in chromatin accessibility and
were correlated with gene expression differences across regions
and gestational ages. We identified two functional de novo
variants in a pRE for autism risk gene SLC6A1, and using CRISPRa,
demonstrated that this pRE regulates SCL6A1. Additionally, mouse
transgenic experiments validated enhancer activity for pREs
proximal to FEZF2 and BCL11A. Thus, this atlas serves as a
resource for decoding neurodevelopmental gene regulation in
health and disease.",
journal = "Cell",
volume = 182,
number = 3,
pages = "754--769.e18",
month = jun,
year = 2020,
keywords = "ATAC-seq; autism; chromatin; enhancers; gene regulation; machine
learning; neurodevelopment; neuropsychiatric disorders",
language = "en"
}
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L"],"bibdata":{"bibtype":"article","type":"article","title":"A Chromatin Accessibility Atlas of the Developing Human Telencephalon","author":[{"propositions":[],"lastnames":["Markenscoff-Papadimitriou"],"firstnames":["Eirene"],"suffixes":[]},{"propositions":[],"lastnames":["Whalen"],"firstnames":["Sean"],"suffixes":[]},{"propositions":[],"lastnames":["Przytycki"],"firstnames":["Pawel"],"suffixes":[]},{"propositions":[],"lastnames":["Thomas"],"firstnames":["Reuben"],"suffixes":[]},{"propositions":[],"lastnames":["Binyameen"],"firstnames":["Fadya"],"suffixes":[]},{"propositions":[],"lastnames":["Nowakowski"],"firstnames":["Tomasz","J"],"suffixes":[]},{"propositions":[],"lastnames":["Kriegstein"],"firstnames":["Arnold","R"],"suffixes":[]},{"propositions":[],"lastnames":["Sanders"],"firstnames":["Stephan","J"],"suffixes":[]},{"firstnames":[],"propositions":[],"lastnames":["State, Matthew W"],"suffixes":[]},{"propositions":[],"lastnames":["Pollard"],"firstnames":["Katherine","S"],"suffixes":[]},{"propositions":[],"lastnames":["Rubenstein"],"firstnames":["John","L"],"suffixes":[]}],"abstract":"To discover regulatory elements driving the specificity of gene expression in different cell types and regions of the developing human brain, we generated an atlas of open chromatin from nine dissected regions of the mid-gestation human telencephalon, as well as microdissected upper and deep layers of the prefrontal cortex. We identified a subset of open chromatin regions (OCRs), termed predicted regulatory elements (pREs), that are likely to function as developmental brain enhancers. pREs showed temporal, regional, and laminar differences in chromatin accessibility and were correlated with gene expression differences across regions and gestational ages. We identified two functional de novo variants in a pRE for autism risk gene SLC6A1, and using CRISPRa, demonstrated that this pRE regulates SCL6A1. Additionally, mouse transgenic experiments validated enhancer activity for pREs proximal to FEZF2 and BCL11A. Thus, this atlas serves as a resource for decoding neurodevelopmental gene regulation in health and disease.","journal":"Cell","volume":"182","number":"3","pages":"754–769.e18","month":"June","year":"2020","keywords":"ATAC-seq; autism; chromatin; enhancers; gene regulation; machine learning; neurodevelopment; neuropsychiatric disorders","language":"en","bibtex":"@ARTICLE{Markenscoff-Papadimitriou2020-bc,\n title = \"A Chromatin Accessibility Atlas of the Developing Human\n Telencephalon\",\n author = \"Markenscoff-Papadimitriou, Eirene and Whalen, Sean and Przytycki,\n Pawel and Thomas, Reuben and Binyameen, Fadya and Nowakowski,\n Tomasz J and Kriegstein, Arnold R and Sanders, Stephan J and\n {State, Matthew W} and Pollard, Katherine S and Rubenstein, John\n L\",\n abstract = \"To discover regulatory elements driving the specificity of gene\n expression in different cell types and regions of the developing\n human brain, we generated an atlas of open chromatin from nine\n dissected regions of the mid-gestation human telencephalon, as\n well as microdissected upper and deep layers of the prefrontal\n cortex. We identified a subset of open chromatin regions (OCRs),\n termed predicted regulatory elements (pREs), that are likely to\n function as developmental brain enhancers. pREs showed temporal,\n regional, and laminar differences in chromatin accessibility and\n were correlated with gene expression differences across regions\n and gestational ages. We identified two functional de novo\n variants in a pRE for autism risk gene SLC6A1, and using CRISPRa,\n demonstrated that this pRE regulates SCL6A1. Additionally, mouse\n transgenic experiments validated enhancer activity for pREs\n proximal to FEZF2 and BCL11A. Thus, this atlas serves as a\n resource for decoding neurodevelopmental gene regulation in\n health and disease.\",\n journal = \"Cell\",\n volume = 182,\n number = 3,\n pages = \"754--769.e18\",\n month = jun,\n year = 2020,\n keywords = \"ATAC-seq; autism; chromatin; enhancers; gene regulation; machine\n learning; neurodevelopment; neuropsychiatric disorders\",\n language = \"en\"\n}\n\n","author_short":["Markenscoff-Papadimitriou, E.","Whalen, S.","Przytycki, P.","Thomas, R.","Binyameen, F.","Nowakowski, T. J","Kriegstein, A. R","Sanders, S. J","State, Matthew W","Pollard, K. S","Rubenstein, J. 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