caa a22 4500 606190570 CHVBK 20210128100855.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10577-015-9479-3 doi (NATIONALLICENCE)springer-10.1007/s10577-015-9479-3 Two novel DXZ4-associated long noncoding RNAs show developmental changes in expression coincident with heterochromatin formation at the human ( Homo sapiens ) macrosatellite repeat [Elektronische Daten] [Debbie Figueroa, Emily Darrow, Brian Chadwick] On the male X and female active X chromosome (Xa), the macrosatellite repeat (MSR) DXZ4 is packaged into constitutive heterochromatin characterized by CpG methylation and histone H3 tri-methylated at lysine-9 (H3K9me3). In contrast, DXZ4 on the female inactive X chromosome (Xi), is packaged into euchromatin, is bound by the architectural protein CCCTC-binding factor, and mediates Xi-specific long-range cis contact with similarly packaged tandem repeats on the Xi. In cancer, male DXZ4 can inappropriately revert to a Xi-like state and other MSRs have been reported to adopt alternate chromatin configurations in response to disease. Given this plasticity, we sought to identify factors that might control heterochromatin at DXZ4. In human embryonic stem cells, we found low levels of 5-hydroxymethylcytosine at DXZ4 and that this mark is lost upon differentiation as H3K9me3 is acquired. We identified two previously undescribed DXZ4 associated noncoding transcripts (DANT1 and DANT2) that are transcribed toward DXZ4 from promoters flanking the array. Each generates transcript isoforms that traverse the MSR. However, upon differentiation, enhancer of Zeste-2 silences DANT1, and DANT2 transcription terminates prior to entering DXZ4. These data support a model wherein DANT1 and/or DANT2 may function to regulate constitutive heterochromatin formation at this MSR. Springer Science+Business Media Dordrecht, 2015 Macrosatellite nationallicence DXZ4 nationallicence X chromosome inactivation nationallicence Human embryonic stem cells nationallicence Euchromatin and heterochromatin nationallicence Long noncoding RNA nationallicence 5-hmC : 5′-Hydoxymethylcytosine nationallicence 5-mC : 5′-Methylcytosine nationallicence ATCC : American Type Culture Collection nationallicence ATT : Array-traversing transcript nationallicence BiS : Bisulfite sequencing nationallicence CGI : CpG island nationallicence ChIP : Chromatin immunoprecipitation nationallicence CTCF : CCCTC-binding factor nationallicence DANT1 : DXZ4-associated noncoding transcript, proximal nationallicence DANT2 : DXZ4-associated noncoding transcript, distal nationallicence dsRNA : Double-stranded RNA nationallicence EBOGs : Embryoid body out-growths nationallicence EZH2 : Enhancer of Zeste 2 nationallicence ESTs : Expressed sequence tags nationallicence FSHD : Facioscapulohumeral muscular dystrophy nationallicence H3K4me2 : Histone H3 di-methylated at lysine 4 nationallicence H3K9me3 : Histone H3 tri-methyated at lysine 9 nationallicence hESCs : Human embryonic stem cells nationallicence HGNC : Human Gene Nomenclature Committee nationallicence kb : Kilobases nationallicence LINE : Long interspersed elements nationallicence IncRNA : Long noncoding RNA nationallicence LTR : Long terminal repeats nationallicence mRNA : Messenger RNA nationallicence MSR : Macrosatellite repeat nationallicence ORF : Open reading frame nationallicence oxBiS : Oxidative bisulfite sequencing nationallicence PBS : Phosphate-buffered saline nationallicence PRC2 : Polycomb repressive complex 2 nationallicence qChIP : Quantitative chromatin immunoprecipitation nationallicence qPCR : Quantitative PCR nationallicence RACE : Rapid amplification of cDNA ends nationallicence RT-PCR : Reverse transcription PCR nationallicence SR : Simple repeat nationallicence SSC : Saline-sodium citrate nationallicence TSS : Transcription start sites nationallicence Xa : Active X chromosome nationallicence XCI : X chromosome inactivation nationallicence Xi : Inactive X chromosome nationallicence XIST : X inactive specific transcript nationallicence Figueroa Debbie Department of Biological Science, Florida State University, 319 Stadium Drive, King 3076, 32306-4295, Tallahassee, FL, USA aut Darrow Emily Department of Biological Science, Florida State University, 319 Stadium Drive, King 3076, 32306-4295, Tallahassee, FL, USA aut Chadwick Brian Department of Biological Science, Florida State University, 319 Stadium Drive, King 3076, 32306-4295, Tallahassee, FL, USA aut Chromosome Research Springer Netherlands 23/4(2015-12-01), 733-752 0967-3849 23:4<733 2015 23 10577 https://doi.org/10.1007/s10577-015-9479-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10577-015-9479-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Figueroa Debbie Department of Biological Science, Florida State University, 319 Stadium Drive, King 3076, 32306-4295, Tallahassee, FL, USA aut NATIONALLICENCE 700 1- Darrow Emily Department of Biological Science, Florida State University, 319 Stadium Drive, King 3076, 32306-4295, Tallahassee, FL, USA aut NATIONALLICENCE 700 1- Chadwick Brian Department of Biological Science, Florida State University, 319 Stadium Drive, King 3076, 32306-4295, Tallahassee, FL, USA aut NATIONALLICENCE 773 0- Chromosome Research Springer Netherlands 23/4(2015-12-01), 733-752 0967-3849 23:4<733 2015 23 10577