{"ID": "doi:10.1101/2021.06.01.446655", "lab": {"@id": "/labs/karen-adelman-lab/", "status": "current", "display_title": "Karen Adelman, HARVARD", "@type": ["Lab", "Item"], "title": "Karen Adelman, HARVARD", "uuid": "0aae4b45-b6de-45da-84e6-738667c36f03", "correspondence": [{"contact_email": "a2FyZW5fYWRlbG1hbkBobXMuaGFydmFyZC5lZHU=", "@id": "/users/59826b1d-7f8b-484f-bfba-8e29f57169d2/", "display_title": "Karen Adelman"}], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "submits_for.0aae4b45-b6de-45da-84e6-738667c36f03"]}}, "url": "http://biorxiv.org/lookup/doi/10.1101/2021.06.01.446655", "award": {"uuid": "619535d9-ec49-4f36-9cad-a0887cf535cb", "name": "TCPA-2017-01", "@id": "/awards/TCPA-2017-01/", "project": "4DN", "center_title": "TCPA - Adelman", "description": "TCPA: \u200bThere is a clear relationship between nuclear genome organization and the regulation of gene expression, and a great deal of effort has been dedicated to defining the effects of genome architecture on gene activity. Herein, we propose to complement this work by approaching the relationship from the other direction. We will ask: how does nascent RNA synthesis from enhancers and promoters impact genome organization? Our specific hypothesis is that nascent RNA plays a central role in stabilizing transient promoter-enhancer contacts that occur within topologically-associated domains (TADs), and thus facilitates the communication between distal cis-regulatory regions. This idea is supported by recent demonstrations that nascent RNA can serve as a platform for the recruitment and retention of transcription factors and epigenetic modifiers. Accordingly, several studies have suggested roles for specific enhancer RNAs in the establishment or maintenance of three-dimensional (3D) enhancer-promoter loops and associated gene activity. However, a full appreciation for the role of nascent RNA synthesis on \ngenome structure will require a more rigorous, coordinated and comprehensive approach than has been carried out to date. We therefore propose a collaborative project within the framework of the 4D Nucleome network to address how enhancer and gene transcription impact chromosome organization.", "display_title": "ELUCIDATING THE ROLE OF NASCENT RNA IN ENHANCER-PROMOTER COMMUNICATION AND THREE-DIMENSIONAL GENOME ORGANIZATION", "status": "current", "@type": ["Award", "Item"], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Screening thousands of transcribed coding and non-coding regions reveals sequence determinants of RNA polymerase II elongation potential", "status": "current", "aliases": ["4dn-dcic-lab:biorxiv_adelman-lab_chipseq-confluent-mESCs"], "authors": ["Vlaming H", "Mimoso CA", "Martin BJ", "Field AR", "Adelman K"], "journal": "bioRxiv", "version": "1", "abstract": "Organismal growth and development rely on RNA Polymerase II (RNAPII) synthesizing the appropriate repertoire of messenger RNAs (mRNAs) from protein-coding genes. Productive elongation of full-length transcripts is essential for mRNA function, however what determines whether an engaged RNAPII molecule will terminate prematurely or transcribe processively remains poorly understood. Notably, despite a common process for transcription initiation across RNAPII-synthesized RNAs1, RNAPII is highly susceptible to termination when transcribing non-coding RNAs such as upstream antisense RNAs (uaRNAs) and enhancers RNAs (eRNAs)2, suggesting that differences arise during RNAPII elongation. To investigate the impact of transcribed sequence on elongation potential, we developed a method to screen the effects of thousands of INtegrated Sequences on Expression of RNA and Translation using high-throughput sequencing (INSERT-seq). We found that higher AT content in uaRNAs and eRNAs, rather than specific sequence motifs, underlies the propensity for RNAPII termination on these transcripts. Further, we demonstrate that 5 splice sites exert both splicing-dependent and autonomous, splicing-independent stimulation of transcription, even in the absence of polyadenylation signals. Together, our results reveal a potent role for transcribed sequence in dictating gene output at mRNA and non-coding RNA loci, and demonstrate the power of INSERT-seq towards illuminating these contributions.", "date_created": "2021-06-23T19:12:14.228666+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2022-02-27T09:53:29.180731+00:00"}, "date_published": "2021-06-01", "public_release": "2021-07-06", "schema_version": "2", "project_release": "2021-07-06", "exp_sets_prod_in_pub": [{"@id": "/experiment-set-replicates/4DNESQ33L4G7/", "display_title": "4DNESQ33L4G7", "accession": "4DNESQ33L4G7", "uuid": "e7b8e1d0-9cb7-4d68-b435-e37c4696ef49", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "experimentset_type": "replicate", "status": "released", "experiments_in_set": [{"display_title": "ChIP-seq against H3K27ac (mouse) on F121-9-CASTx129 (Tier 2) - 4DNEXH9N86AA", "@id": "/experiments-seq/4DNEXH9N86AA/", "@type": ["ExperimentSeq", "Experiment", "Item"], "uuid": "85d365d5-ab4e-40ab-a402-3b092421fe94", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "experiment_type": {"title": "ChIP-seq", "@type": ["ExperimentType", "Item"], "@id": "/experiment-types/chip-seq/", "status": "released", "display_title": "ChIP-seq", "uuid": "47a593da-c458-422a-a974-82b3302e89cb", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"display_title": "ChIP-seq against H3K27ac (mouse) on F121-9-CASTx129 (Tier 2) - 4DNEXLI3BRQH", "@id": "/experiments-seq/4DNEXLI3BRQH/", "@type": ["ExperimentSeq", "Experiment", "Item"], "uuid": "ed9a4f4c-3ead-41fe-9bf3-6424ab5af633", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "experiment_type": {"title": "ChIP-seq", "@type": ["ExperimentType", "Item"], "@id": "/experiment-types/chip-seq/", "status": "released", "display_title": "ChIP-seq", "uuid": "47a593da-c458-422a-a974-82b3302e89cb", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@id": "/publications/5d4f2c86-bd45-422f-b787-f04f2c9c12c6/", "@type": ["Publication", "Item"], "uuid": "5d4f2c86-bd45-422f-b787-f04f2c9c12c6", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Vlaming H et al. (2021) doi:10.1101/2021.06.01.446655", "external_references": [], "short_attribution": "Vlaming H et al. (2021)", "number_of_experiment_sets": 1, "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}