Journal of Cell Science aaaa2009,Japan 240-0193, Kanagawa Japan 981-8555, Sendai o:10.1242/jcs.103903 doi: 3739–3744 125, Science Cell of Journal 2012 April 3 Accepted ncikncl nuclei chromatin cell of chicken variant positioning in histone spatial for the required and are Arp6 H2A.Z member family actin The Report Short htocp iceedmis(rmre l,20;Msei 2007). Misteli, 2006; al., et (Cremer nucleus, domains (CTs) discrete are the territories occupy the chromosome that of genome form of regions the chromosomes interphase structure compartmentalized of and physical spatially regions in the functional located to vertebrates, In organization genome. of level further Wong 2006; al., et 2007). Ruhl yeasts al., 2004; in al., et both et of H2A.Z (Mizuguchi variant replacement vertebrates the the and with catalyzes H2A which histone 2010), nucleosomal al., SWR1/SRCAP al., and et et the Yoshida Wu Oma 2004; nucleus of 2005; al., et component the 2006; (Mizuguchi complex essential in al., remodeling an chromatin al., localized et as et predominantly identified Ohfuchi Dion is and 2009; 2007; Arp6 Shen, 2011). al., Harata, and of et (Chen components Meagher complexes essential 2010; of these are actin of organization modification (Arps), of some the consists proteins which to histone actin-related family, actin respect and the with and of Members roles chromatin. key remodeling play complexes chromatin Various Introduction different the through for insufficient CTs is of se distribution per periphery radial nuclear the the words: to to Key gene-poor chromatin contribute for of extent H2A.Z lesser localization genes. to and The the most but chromatin. that of Arp6 is microchromosomes, into suggested repression Arp6 gene-rich H2A.Z that analysis cells. variant for knockout indicate Microarray histone cells these the H2A.Z-deficient mechanisms. in results deposits in impaired which These was observed is complex, CTs also macrochromosomes. of remodeling which it and was in distribution chromatin gene-dense structure, CTs cells radial SRCAP cells, of DT40 chromatin the vertebrate the chicken redistribution that of of analyzed of showed We nucleus component alteration and respectively. interphase essential conditionally, local periphery, the an out and normal the In center knocked of chromatin. the been in differentiation of in had the roles located positioning Arp6 during are spatial have (CTs) altered the (Arps) territories is in chromosome and proteins involved gene-poor function are actin-related genome they nuclear to whether contributes Although unclear nucleus cells. the tumorigenic in chromatin and of organization spatial The Summary work this to equally ` contributed authors *These 7 6 5 4 3 2 1 Maruyama Ohfuchi Eri asoFukagawa Tatsuo hgnb Tone Shigenobu uhr o orsodne( correspondence for Authors eateto ilg fteCl ulu,Isiueo oeua eeis SC,vvi,Pau 42,CehRepublic Czech Germany 14220, Mainz, 4 55128 Prague 4, v.v.i., Ackermannweg CR, (IMB), AS gGmbH Genetics, Biology Molecular Molecular of of Institute Institute Germany Nucleus, (Sokendai), Munich, Cell Studies Japan 80539 the Advanced 701-0192, Ludwig-Maximilians-University, Japan of for Kurashiki 411-8540, Biology University School, Shizuoka of Graduate Medical Studies, Department The Kawasaki Advanced Sciences, Biochemistry, for Advanced of University of Department Graduate School The Biosystems, and of Genetics Studies Aoba-ku, of Evolutionary 1-1, Institute of Tsutsumidori-Amamiyamachi National Department University, Genetics, Tohoku Molecular Science, of Agricultural Department of School Graduate Biology, Molecular of Laboratory 02 ulse yTeCmayo ilgssLtd Biologists of Company The by Published 2012. h pta ragmn fcrmtni h ulu dsa adds nucleus the in chromatin of arrangement spatial The ci-eae rti,Hsoevrat ula raiain hoooetrioy eeexpression Gene territory, Chromosome organization, Nuclear variant, Histone protein, Actin-related 4 ae Hozak Pavel , 2 [email protected] n aaioHarata Masahiko and 1, ,TtuaHori Tetsuya *, 5 ei .Habermann A. Felix , ; [email protected] 2, ,Hdyk Tanabe Hideyuki *, 1, ` 6 oanvnHase von Johann , ) ta. 06 ue l,20;Lee l,20;Ysiae al., et Yoshida 2007; al., et Lee 2008; (Chuang al., be organization et to chromatin Hu suggested of 2006; al., are levels the et Arps higher in for Although chromatin required limited. of arrangement remains spatial nucleus the about al., information et Wiech 2008; Misteli, and Meaburn cells 2005). 2003; cancer al., of 2007; types et multiple Misteli, in (Cremer and and by 2006), (Meaburn Misteli, supported development and Meshorer during types, is tissue altered and CTs cell is to physiological of and specific is distribution The arrangement their respectively. radial that evidence the nucleus, center of the the significance of in periphery positioned microchromosomes are gene-rich and macrochromosomes this of gene-poor territories within 2005). the and al., CTs cells, et Gilbert chicken of 2001; In Cremer, position al., and Cremer et The and 1998; (Bridger Croft Bickmore, density 1999). gene 2001; with al., correlated al., is et arrangement polarized et (Boyle nucleus center Sadoni the the from 1999; of arrangement periphery polarized a the of to in part distribution, is radial CT a each have which usually nucleus interphase the in CTs ept ayrcn tde fcrmtnorganization, chromatin of studies recent many Despite 3, ` ioh Kitamura Hiroshi , 7 hitp Cremer Christoph , 1, ,RoMatsuda Ryo *, 7 , 1 , 3739 Journal of Cell Science eefudpeoiatya h eihr ftences n the and nucleus, the of (red) periphery macrochromosomes the at the predominantly 2002b), Tanabe found al., 2001; were et al., Tanabe et 2002a; preserved al., (Habermann three-dimensionally et previously with reported pools As hybridized The nuclei. microchromosomes. were of probes pairs 21 one of detect probes, to other Z) of and the 1–8 and of pools (chromosomes macrochromosomes two types detect to using two designed of visualized These situ distribution were territories. in spatial chromosomes microchromosome al., the fluorescence et and analyze Tanabe three-dimensional macro- to 2002a; the (3D-FISH) al., used hybridization et Tanabe We respectively 2001; chromatin, 2002b). are al., gene-rich et which and (Habermann gene-poor microchromosomes, of and composed (supplementary macrochromosomes tet into of addition the after significantly S2). not Fig. hr did material cells 144 dead of until number the increase the wild- of that with stage and comparison in cells, each changed type at significantly not cells was Arp6-deficient cycle until cell of tet with distribution revealed analysis treated the FACS not S1D). that cells Fig. material the (supplementary (supplementary as hr well 96 tet as of proliferated the tet addition Consistently, with the S1B,C). after Fig. became hr protein material Arp6 96 in and by tet, Arp6 to undetectable of exposure upon expression reduced the western was cells that and showed Northern analyses promoter. blot (tet)-repressible In the tetracycline the S1A). of a expression Fig. using the material Arp6 cells, (supplementary KO line for the cell cells B and DT40 (KO) constructed chicken we knockout Arp6, conditional of function analyzed cellular the investigate To cells chromosome Arp6-deficient of in distribution spatial territories radial the the of in Impairment Discussion function and their Results about nucleus. the unclear in CTs still of is positioning it 2010), 3740 hce hoooe r lsiido h ai ftersize their of basis the on classified are chromosomes Chicken ora fCl cec 2 (16) 125 Science Cell of Journal ARP6 ARP6 eewscnrle by controlled was gene K el treated cells -KO ARP6 -KO hwdta hs ifrne eesaitclysignificant statistically were differences these ( as Mann–Whitney The that outwards 2). 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Bridger, S., Gilchrist, S., Boyle, References number at http://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.103903/-/DC1 online available [grant material Supplementary Fellow) Research Young for (JSPS Republic (JSPS) Science 225962]. supported Czech Integrated of Fellowships was Promotion the of H.K. the of for Scientist P.H.]. Promotion Society to MEYS Japan the LH12143 the and by and for H.T.; LC545 Center numbers to [grant the Advanced Sokendai for and of Center Science of H.T. Hayama the to Ministry a from T.H.]; Studies Projects to the 23114722 Research [grant M.H., for from Japan to grant 21114503 Technology, Grant-in-Aids H.T., to and 23125505 by Science, numbers Sports, funded Culture, was Education, work This Funding GeneChip the by operated were 1.3. analyses Manual GeneChip Software data Affymetrix and Operating Technical an systems using These Analysis 7G. read 3000 were Expression Scanner GeneChips synthesized latex The GeneChip was USA). 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DNA TGS the of 3.1 were images CTs AMIRA thresholded the from Oberkochen, for using reconstructed Zeiss, stacks by image Carl of generated META, reconstructions (LSM510 Three-dimensional microscope Germany). confocal scanning laser eerglto nmmaincells. mammalian in regulation gene est-eae ihrodrcrmtnarneet nnra n uo elnuclei. cell tumor and Biol. normal Cell in T. J. arrangements Cremer, chromatin and order R. higher M. density-related Speicher, J., Diebold, L., Kreja, site. S. chromosome A. Belmont, 20) h pta raiaino ua hoooe ihntence fnormal of nuclei the within chromosomes cells. human emerin-mutant of and organization spatial The (2001). dynamics. Genet. state. transcriptional previous of memory epigenetic confers H. J. Brickner, and 14 403-409. , ur pn elBiol. Cell Opin. Curr. 162 pe,K,Wge,B,Wzla,L,vnHs,J,Wiad Y., Weiland, J., Hase, von L., Wizelman, B., Wagler, K., ¨pper, 809-820. , ur Biol. Curr. 20) ogrnedrcinlmvmn fa interphase an of movement directional Long-range (2006). 20) 2.-eitdlocalizatio H2A.Z-mediated (2007). 20) ula ci n ci-eae rtisi chromatin in proteins actin-related and actin Nuclear (2007). u.Ml Genet. Mol. Hum. 20) hoooetriois ula rhtcueand architecture nuclear territories, Chromosome (2001). 16 825-831. , 19 326-330. , 19) utn h eoeo h map. the on genome the Putting (1998). a.Rv Genet. Rev. Nat. 10 211-219. , fgnsa h ula periphery nuclear the at genes of n 2 292-301. , LSBiol. PLoS 20) neiac fgene of Inheritance (2003). U -test. 5 ,e81. Trends oeo r6adHAZi ula raiain3743 organization nuclear in H2A.Z and Arp6 of Role aemn,F . rmr . atr . rt,G,vnHs,J,Bur K., Bauer, J., Hase, Schu von L., G., Harewood, Kreth, J., Walter, M., Cremer, A., F. Habermann, rfi,D . aemn . aaad,J,OBin . ag,M,Sznv A., Sazanov, M., Bagga, P., O’Brien, J., Masabanda, F., Haberman, K., D. Griffin, ibr,N,Glhit .adBcmr,W A. W. Bickmore, and S. Gilchrist, N., Gilbert, M. S. 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Oma, u . wn .S,Nnz . admn,M . ut .R,Og,K A., K. Ohgi, R., K. Hutt, D., M. Cardamone, E., Nunez, S., Y. Kwon, Q., Hu, iuuh,G,Se,X,Lnr,J,W,W . e,S n u C. Wu, and S. Sen, H., W. Wu, J., Landry, X., Shen, G., Mizuguchi, E. Roy, and C. E. McKinney, K., M. Kandasamy, B., R. Meagher, T. Misteli, and J. K. Meaburn, Harata, T. Misteli, and and T. J. K. Fukagawa, Meaburn, K., Takeuchi, H., Kitamura, Kwon, and T., H. Hori, J. Lim, R., W., K. Matsuda, Kim, K., Y. Kwon, J., S. Kwon, J., M. Kang, K., Lee, L. D. Spector, and I. R. Kumaran, itl,T. Misteli, T. Misteli, and E. Meshorer, T. Misteli, and J. S. Lockett, S., Khan, R., P. Gudla, J., K. Meaburn, Ku pe,K,Ko K., ¨pper, ineg . rmr . rmr .adSlvi I. Solovei, cells. and chicken T. in microchromosomes Cremer, and C., macro- Cremer, J., Wienberg, eeexpression. gene A. Reymond, tools microdissection: and genome. chicken cytometry the flow J. mapping by Wienberg, for and generated M. paints Ferguson-Smith, W., macrochromosome D. 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