An Expanded Registry of Candidate cis-Regulatory Elements for Studying Transcriptional Regulation Article Swipe

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Jill E. Moore , Henry Pratt , Kaili Fan , Nishigandha Phalke , Jonathan Fisher , Shaimae I. Elhajjajy , Gregory Andrews , Mingshi Gao , Nicole Shedd , Yu Fu , Matthew C Lacadie , Jane L. Meza , Mohit Ganna , Eva Choudhury , Ross Swofford , Nina Farrell , Anusri Pampari , Vivekanandan Ramalingam , Fairlie Reese , Beatrice Borsari , X. Yu , Eve S. Wattenberg , Marina Ruiz‐Romero , Milad Razavi-Mohseni , Jinrui Xu , Timur R. Galeev , M Beer , Roderic Guigó , Mark Gerstein , J Engreitz , Mats Ljungman , Timothy E. Reddy , M Snyder , Charles B. Epstein , Elizabeth Gaskell , B Bernstein , Diane E. Dickel , Axel Visel , L Pennacchio , A Mortazavi , Anshul Kundaje , Zhiping Weng ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1101/2024.12.26.629296

Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. Previously, The ENCODE consortium mapped biochemical signals across many cell types and tissues and integrated these data to develop a Registry of 0.9 million human and 300 thousand mouse candidate cis-Regulatory Elements (cCREs) annotated with potential functions 1 . We have expanded the Registry to include 2.35 million human and 927 thousand mouse cCREs, leveraging new ENCODE datasets and enhanced computational methods. This expanded Registry covers hundreds of unique cell and tissue types, providing a comprehensive understanding of gene regulation. Functional characterization data from assays like STARR-seq, MPRA, CRISPR perturbation, and transgenic mouse assays now cover over 90% of human cCREs, revealing complex regulatory functions. We identified thousands of novel silencer cCREs and demonstrated their dual enhancer/silencer roles in different cellular contexts. Integrating the Registry with other ENCODE annotations facilitates genetic variation interpretation and trait-associated gene identification, exemplified by discovering KLF1 as a novel causal gene for red blood cell traits. This expanded Registry is a valuable resource for studying the regulatory genome and its impact on health and disease.

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Computational Biology

Biology

Human Genome

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ENCODE Enhancer Computational biology Biology Regulatory sequence Gene Genome Human genome Genetics Regulation of gene expression Transcription factor

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2024.12.26.629296
OA Status: green
Cited By: 8
References: 72
Related Works: 10
OpenAlex ID: https://openalex.org/W4405808443

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DOI: https://doi.org/10.1101/2024.12.26.629296

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Title: An Expanded Registry of Candidate cis-Regulatory Elements for Studying Transcriptional Regulation

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Language: en

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Publication year: 2024

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Publication date: 2024-12-26

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Authors: Jill E. Moore, Henry Pratt, Kaili Fan, Nishigandha Phalke, Jonathan Fisher, Shaimae I. Elhajjajy, Gregory Andrews, Mingshi Gao, Nicole Shedd, Yu Fu, Matthew C Lacadie, Jane L. Meza, Mohit Ganna, Eva Choudhury, Ross Swofford, Nina Farrell, Anusri Pampari, Vivekanandan Ramalingam, Fairlie Reese, Beatrice Borsari, X. Yu, Eve S. Wattenberg, Marina Ruiz‐Romero, Milad Razavi-Mohseni, Jinrui Xu, Timur R. Galeev, M Beer, Roderic Guigó, Mark Gerstein, J Engreitz, Mats Ljungman, Timothy E. Reddy, M Snyder, Charles B. Epstein, Elizabeth Gaskell, B Bernstein, Diane E. Dickel, Axel Visel, L Pennacchio, A Mortazavi, Anshul Kundaje, Zhiping Weng

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Concepts: ENCODE, Enhancer, Computational biology, Biology, Regulatory sequence, Gene, Genome, Human genome, Genetics, Regulation of gene expression, Transcription factor

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Cited by: 8

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abstract_inverted_index.exemplified	153
abstract_inverted_index.expression.	15
abstract_inverted_index.facilitates	145
abstract_inverted_index.regulation.	95
abstract_inverted_index.demonstrated	129
abstract_inverted_index.comprehensive	91
abstract_inverted_index.computational	76
abstract_inverted_index.perturbation,	105
abstract_inverted_index.understanding	92
abstract_inverted_index.cis-Regulatory	46
abstract_inverted_index.interpretation	148
abstract_inverted_index.identification,	152
abstract_inverted_index.characterization	97
abstract_inverted_index.trait-associated	150
abstract_inverted_index.enhancer/silencer	132
cited_by_percentile_year.max	99
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corresponding_author_ids	https://openalex.org/A5079819085
countries_distinct_count	3
institutions_distinct_count	42
corresponding_institution_ids	https://openalex.org/I166722992
citation_normalized_percentile.value	0.9043419
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	True