{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:07:38Z","timestamp":1786133258138,"version":"build-2736575974"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770658"],"award-info":[{"award-number":["81770658"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070689"],"award-info":[{"award-number":["82070689"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010041","name":"Tianjin Municipal Science and Technology Commission","doi-asserted-by":"crossref","award":["19JCJQJC63800"],"award-info":[{"award-number":["19JCJQJC63800"]}],"id":[{"id":"10.13039\/501100010041","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>\n                      Transcription factors (TFs) play crucial roles in kidney development and diseases by recognizing specific DNA sequences to control gene expression programs. The kidney\u2019s cellular heterogeneity poses substantial challenges to identifying the genomic binding sites and direct target genes of TFs\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . We apply the cleavage under targets and release using nuclease (CUT&amp;RUN) technique, together with transcriptomic analysis, to identify cAMP response element-binding protein (CREB) target genes in cystic epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) in a mouse model. CREB binds to and activates ribosomal biogenesis genes, and inhibition of CREB retards cyst growth in the ADPKD models. CUT&amp;RUN is a powerful method for genome-scale profiling and identifying direct targets of TFs from small numbers of specific kidney cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Genome-wide mapping of transcription factor (TF) binding sites is essential to identify a TF\u2019s direct target genes in kidney development and diseases. However, due to the cellular complexity of the kidney and limited numbers of a given cell type, it has been challenging to determine the binding sites of a TF\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . cAMP response element-binding protein (CREB) is phosphorylated and hyperactive in autosomal dominant polycystic kidney disease (ADPKD). We focus on CREB as an example to profile genomic loci bound by a TF and to identify its target genes using low numbers of specific kidney cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cleavage under targets and release using nuclease (CUT&amp;RUN) assays were performed with\n                      <jats:italic toggle=\"yes\">Dolichos biflorus<\/jats:italic>\n                      agglutinin (DBA)\u2013positive tubular epithelial cells from normal and ADPKD mouse kidneys. Pharmacologic inhibition of CREB with 666-15 and genetic inhibition with A-CREB were undertaken using ADPKD mouse models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CUT&amp;RUN to profile genome-wide distribution of phosphorylated CREB (p-CREB) indicated correlation of p-CREB binding with active histone modifications (H3K4me3 and H3K27ac) in cystic epithelial cells. Integrative analysis with CUT&amp;RUN and RNA-sequencing revealed CREB direct targets, including genes involved in ribosome biogenesis and protein synthesis. Pharmacologic and genetic inhibition of CREB suppressed cyst growth in ADPKD mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CREB promotes cystogenesis by activating ribosome biogenesis genes. CUT&amp;RUN, coupled with transcriptomic analysis, enables interrogation of TF binding and identification of direct TF targets from a low number of specific kidney cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021010101","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T18:25:17Z","timestamp":1624472717000},"page":"2529-2541","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Integrative Cistromic and Transcriptomic Analyses Identify CREB Target Genes in Cystic Renal Epithelial Cells"],"prefix":"10.1681","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-338X","authenticated-orcid":false,"given":"Zhiheng","family":"Liu","sequence":"first","affiliation":[{"name":"2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China"},{"name":"Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjing","family":"Liu","sequence":"additional","affiliation":[{"name":"2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Dang","sequence":"additional","affiliation":[{"name":"2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijuan","family":"Geng","sequence":"additional","affiliation":[{"name":"2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhan","family":"Sun","sequence":"additional","affiliation":[{"name":"2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongze","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8887-9547","authenticated-orcid":false,"given":"Yupeng","family":"Chen","sequence":"additional","affiliation":[{"name":"2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, 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