title: CTCF-mediated Chromatin Loop for the Posterior Hoxc Gene Expression in MEF Cells.
abstract: Modulation of chromatin structure has been proposed as a molecular mechanism underlying the spatiotemporal collinear expression of Hox genes during development. CCCTC-binding factor (CTCF)-mediated chromatin organization is now recognized as a crucial epigenetic mechanism for transcriptional regulation. Thus, we examined whether CTCF-mediated chromosomal conformation is involved in Hoxc gene expression by comparing wild-type mouse embryonic fibroblast (MEF) cells expressing anterior Hoxc genes with Akt1 null MEFs expressing anterior as well as posterior Hoxc genes. We found that CTCF binding between Hoxc11 and -c12 is important for CTCF-mediated chromosomal loop formation and concomitant posterior Hoxc gene expression. Hypomethylation at this site increased CTCF binding and recapitulated the chromosomal conformation and posterior Hoxc gene expression patterns observed in Akt1 null MEFs. From this work we found that CTCF at the C12|11 does not function as a barrier/boundary, instead let the posterior Hoxc genes switch their interaction from inactive centromeric to active telomeric genomic niche, and concomitant posterior Hoxc gene expression. Although it is not clear whether CTCF affects Hoxc gene expression solely through its looping activity, CTCF-mediated chromatin structural modulation could be an another tier of Hox gene regulation during development. © 2016 IUBMB Life, 68(6):436-444, 2016.
authors.affiliation: Department of Anatomy, Embryology Laboratory, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyehyun
authors.initials: H
authors.lastname: Min
authors.affiliation: Department of Anatomy, Embryology Laboratory, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoung-Ah
authors.initials: KA
authors.lastname: Kong
authors.affiliation: Department of Anatomy, Embryology Laboratory, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Life Sciences and Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Chang-Pyo
authors.initials: CP
authors.lastname: Hong
authors.affiliation: Department of Life Sciences and Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Seong-Hye
authors.initials: SH
authors.lastname: Seo
authors.affiliation: Department of Life Sciences and Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Roh
authors.affiliation: Department of Pharmacology, MRC For Ischemic Tissue Regeneration, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
authors.affiliation: Department of Anatomy, Embryology Laboratory, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; C000619698:Ctcf protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D004247:DNA; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: CTCF; DNA methylation; Hox genes; Hoxc cluster; chromatin looping; epigenetics