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An ENCODE ChIP-seq pipeline using endogenously tagged human DNA-associated proteins

Award Number: UM1HG009411
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2023

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An ENCODE ChIP-seq pipeline using endogenously tagged human DNA-associated proteins - Project Summary/Abstract Almost a tenth of human genes code for proteins that interact with chromosomes in the nucleus. Most of these DNA-associated proteins (referred to as DAPs) are involved in regulating gene expression, by serving as part of the basic transcriptional machinery, as transcription factors that regulate the spatial and temporal levels of transcription, or as chromatin state regulators. These proteins are key components in biology, as transcriptional regulation underlies fundamental biological processes in organismal development, in determining cell states during differentiation, and in directing physiological responses to the internal and external environment. Thus, comprehensive and detailed assessment of the molecular actions of DAPs, that is, where they interact throughout the human genome, is a fundamental long-term goal of both basic and clinical research. In response to RFA-HG-16-002, “Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Mouse (UM1)”, this application proposes to use a recently-established "shovel ready" pipeline for mapping DAPs in human cell lines that overcomes the very high failure rates of traditional ChIP-seq, a widely- used approach that requires specific antibodies for each factor. The new approach, called CETCh-seq, involves adding an epitope tag at the endogenous locus encoding each protein, and using chromatin immunoprecipitation with a universal antibody against the epitope followed by high-throughput sequencing (ChIP-seq) to identify DAP-DNA associations genome-wide. This production pipeline will be applied to each of 1,244 DAPs that are expressed in a set of human cell lines and have not yet been mapped by ENCODE. During the four-year project, this pipeline will be used to test each of these factors in one human cell line, and for 100 of the DAPs, in four human cell lines, allowing characterization of cell-type differences. The project will also tag and assay multiple allelic versions of a small number of DAPs in which pathogenic or potentially pathogenic mutations have been identified. The project will produce genome-wide DAP maps and identify motifs for hundreds of human regulatory proteins, providing an important component for the next phase of the ENCODE Project. All data, as well as useful materials in the form of gene editing plasmids and tagged human cell lines, will be made freely available to the research community.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$13,625 )
2024	2021	HUDSONALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	000	4	10/16/2023	SUPPLEMENT FOR EXPANSION	-$13,625
														Subtotal = -$13,625

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	001	4	1/7/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2020	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	000	4	1/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $943,115 )
2021	2021	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	001	4	12/18/2020	SUPPLEMENT FOR EXPANSION	$943,115
2021	2020	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	000	4	11/19/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $943,115

Issue Date FY: 2020 ( Subtotal = $1,959,410 )
2020	2020	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	000	4	1/28/2020	NON-COMPETING CONTINUATION	$1,959,410
														Subtotal = $1,959,410

Issue Date FY: 2019 ( Subtotal = $1,959,410 )
2019	2019	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	000	3	1/30/2019	NON-COMPETING CONTINUATION	$1,959,410
														Subtotal = $1,959,410

Issue Date FY: 2018 ( Subtotal = $1,959,410 )
2018	2018	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	001	2	7/10/2018	NON-COMPETING CONTINUATION	$391,881
2018	2018	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	000	2	1/22/2018	NON-COMPETING CONTINUATION	$1,567,529
														Subtotal = $1,959,410

Issue Date FY: 2017 ( Subtotal = $1,959,410 )
2017	2017	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	001	1	7/19/2017	NEW	$548,635
2017	2017	HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY	601 GENOME WAY	HUNTSVILLE	AL	35806	MADISON	USA	Human Genome Research	000	1	2/1/2017	NEW	$1,410,775
														Subtotal = $1,959,410

Grand Total All Awards = $8,767,130

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An ENCODE ChIP-seq pipeline using endogenously tagged human DNA-associated proteins

Award Number: UM1HG009411

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2023

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