@article{SchmidSteinleinYanoetal.2016,
  author    = {Schmid, Michael and Steinlein, Claus and Yano, Cassia F. and Cioffi, Marcelo B.},
  title     = {Hypermethylated Chromosome Regions in Nine Fish Species with Heteromorphic Sex Chromosomes},
  series = {Cytogenetic and Genome Research},
  volume    = {147},
  journal   = {Cytogenetic and Genome Research},
  number    = {2-3},
  issn      = {1424-8581},
  doi       = {10.1159/000444067},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196710},
  pages     = {169-178},
  year      = {2016},
  abstract  = {Sites and amounts of 5-methylcytosine (5-MeC)-rich chromosome regions were detected in the karyotypes of 9 Brazilian species of Characiformes fishes by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. These species, belonging to the genera Leporinus, Triportheus and Hoplias, are characterized by highly differentiated and heteromorphic ZW and XY sex chromosomes. In all species, the hypermethylated regions are confined to constitutive heterochromatin. The number and chromosome locations of hypermethylated heterochromatic regions in the karyotypes are constant and species-specific. Generally, heterochromatic regions that are darkly stained by the C-banding technique are distinctly hypermethylated, but several of the brightly fluorescing hypermethylated regions merely exhibit moderate or faint C-banding. The ZW and XY sex chromosomes of all 9 analyzed species also show species-specific heterochromatin hypermethylation patterns. The analysis of 5-MeC-rich chromosome regions contributes valuable data for comparative cytogenetics of closely related species and highlights the dynamic process of differentiation operating in the repetitive DNA fraction of sex chromosomes.},
  language  = {en}
}
@article{SchmidSteinleinLombetal.2016,
  author    = {Schmid, Michael and Steinlein, Claus and Lomb, Christian and Sperling, Karl and Neitzel, Heidemarie},
  title     = {5-Methylcytosine-Rich Heterochromatin in the Indian Muntjac},
  series = {Cytogenetic and Genome Research},
  volume    = {147},
  journal   = {Cytogenetic and Genome Research},
  number    = {4},
  issn      = {1424-8581},
  doi       = {10.1159/000444431},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196701},
  pages     = {240-246},
  year      = {2016},
  abstract  = {Two 5-methylcytosine (5-MeC)-rich heterochromatic regions were demonstrated in metaphase chromosomes of the Indian muntjac by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. The metaphases were obtained from diploid and triploid cell lines. A major region is located in the 'neck' of the 3;X fusion chromosome and can be detected after denaturation of the chromosomal DNA with UV-light irradiation for 1 h. It is located exactly at the border of the X chromosome and the translocated autosome 3. A minor region is found in the centromeric region of the free autosome 3 after denaturing the chromosomal DNA for 3 h or longer. The structure and possible function of the major hypermethylated region as barrier against spreading of the X-inactivation process into the autosome 3 is discussed.},
  language  = {en}
}
@article{SchmidSteinlein2016,
  author    = {Schmid, Michael and Steinlein, Claus},
  title     = {Chromosome Banding in Amphibia. XXXIII. Demonstration of 5-Methylcytosine-Rich Heterochromatin in Anura},
  series = {Cytogenetic and Genome Research},
  volume    = {148},
  journal   = {Cytogenetic and Genome Research},
  number    = {1},
  issn      = {1424-8581},
  doi       = {10.1159/000446141},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199022},
  pages     = {35-43},
  year      = {2016},
  abstract  = {An experimental approach using monoclonal anti-5-methylcytosine (5-MeC) antibodies and indirect immunofluorescence was elaborated for detecting 5-MeC-rich chromosome regions in anuran chromosomes. This technique was applied to mitotic metaphases of 6 neotropical frog species belonging to 6 genera and 4 families. The hypermethylation patterns were compared with a variety of banding patterns obtained by conventional banding techniques. The hypermethylated DNA sequences are species-specific and located exclusively in constitutive heterochromatin. They are found in centromeric, pericentromeric, telomeric, and interstitial positions of the chromosomes and adjacent to nucleolus organizer regions. 5-MeC-rich DNA sequences can be embedded both in AT- and GC-rich repetitive DNA. The experimental parameters that have major influence on the reproducibility and quality of the anti-5-MeC antibody labeling are discussed.},
  language  = {en}
}
@article{SchmidSteinlein2016,
  author    = {Schmid, Michael and Steinlein, Claus},
  title     = {Chromosome Banding in Amphibia. XXXIV. Intrachromosomal Telomeric DNA Sequences in Anura},
  series = {Cytogenetic and Genome Research},
  volume    = {148},
  journal   = {Cytogenetic and Genome Research},
  number    = {2-3},
  issn      = {1424-8581},
  doi       = {10.1159/000446298},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196693},
  pages     = {211-226},
  year      = {2016},
  abstract  = {The mitotic chromosomes of 4 anuran species were examined by various classical banding techniques and by fluorescence in situ hybridization using a (TTAGGG)\(_n\) repeat. Large intrachromosomal telomeric sequences (ITSs) were demonstrated in differing numbers and chromosome locations. A detailed comparison of the present results with numerous published and unpublished data allowed a consistent classification of the various categories of large ITSs present in the genomes of anurans and other vertebrates. The classification takes into consideration the total numbers of large ITSs in the karyotypes, their chromosomal locations and their specific distribution patterns. A new category of large ITSs was recognized to exist in anuran species. It consists of large clusters of ITSs located in euchromatic chromosome segments, which is in clear contrast to the large ITSs in heterochromatic chromosome regions known in vertebrates. The origin of the different categories of large ITSs in heterochromatic and euchromatic chromosome regions, their mode of distribution in the karyotypes and evolutionary fixation in the genomes, as well as their cytological detection are discussed.},
  language  = {en}
}
@article{NandaSchoriesSimeonovetal.2022,
  author    = {Nanda, Indrajit and Schories, Susanne and Simeonov, Ivan and Adolfi, Mateus Contar and Du, Kang and Steinlein, Claus and Alsheimer, Manfred and Haaf, Thomas and Schartl, Manfred},
  title     = {Evolution of the degenerated Y-chromosome of the swamp guppy, Micropoecilia picta},
  series = {Cells},
  volume    = {11},
  journal   = {Cells},
  number    = {7},
  issn      = {2073-4409},
  doi       = {10.3390/cells11071118},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267242},
  year      = {2022},
  abstract  = {The conspicuous colour sexual dimorphism of guppies has made them paradigmatic study objects for sex-linked traits and sex chromosome evolution. Both the X- and Y-chromosomes of the common guppy (Poecilia reticulata) are genetically active and homomorphic, with a large homologous part and a small sex specific region. This feature is considered to emulate the initial stage of sex chromosome evolution. A similar situation has been documented in the related Endler's and Oropuche guppies (P. wingei, P. obscura) indicating a common origin of the Y in this group. A recent molecular study in the swamp guppy (Micropoecilia. picta) reported a low SNP density on the Y, indicating Y-chromosome deterioration. We performed a series of cytological studies on M. picta to show that the Y-chromosome is quite small compared to the X and has accumulated a high content of heterochromatin. Furthermore, the Y-chromosome stands out in displaying CpG clusters around the centromeric region. These cytological findings evidently illustrate that the Y-chromosome in M. picta is indeed highly degenerated. Immunostaining for SYCP3 and MLH1 in pachytene meiocytes revealed that a substantial part of the Y remains associated with the X. A specific MLH1 hotspot site was persistently marked at the distal end of the associated XY structure. These results unveil a landmark of a recombining pseudoautosomal region on the otherwise strongly degenerated Y chromosome of M. picta. Hormone treatments of females revealed that, unexpectedly, no sexually antagonistic color gene is Y-linked in M. picta. All these differences to the Poecilia group of guppies indicate that the trajectories associated with the evolution of sex chromosomes are not in parallel.},
  language  = {en}
}
@phdthesis{Brocher2007,
  author    = {Brocher, Jan},
  title     = {Einfluss von HMGA1-Proteinen auf die Myogenese und Heterochromatinorganisation w{\"a}hrend der Differenzierung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-24456},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {HMG-Proteine sind nach den Histonen die zweith{\"a}ufigste Superfamilie nukle{\"a}rer Proteine. Sie binden an DNA und Nukleosomen und induzieren strukturelle Ver{\"a}nderungen im Chromatin. Sie spielen eine wichtige Rolle in der Dynamik des Chromatins und beeinflussen dadurch DNA-abh{\"a}ngige Prozesse, wie Transkription und Replikation. Proteine der HMGA-Familie sind charakterisiert durch konservierte DNA-Bindungsmotive, den AT-Hooks, welche eine Bindung an AT-reiche DNA-Sequenzen vermitteln und durch einen sauren C-Terminus. HMGA-Proteine sind verst{\"a}rkt im Heterochromatin konzentriert und stehen in Verbindung mit der Expressionsregulation spezifischer Gene aufgrund der Stabilisierung von Nukleoproteinkomplexen, so genannten Enhanceosomen. HMGA-Proteine spielen des Weiteren eine entscheidende Rolle in verschiedenen Entwicklungsprozessen und bei der Tumorprogression . Um den Einfluss von HMGA1 auf die zellul{\"a}re Differenzierung und die Chromatinmodulation zu untersuchen, wurden C2C12 Maus-Myoblastenzellen verwendet. Die Induktion der Myogenese in diesen Zellen geht mit der Herunterregulierung von HMGA1 einher. Durch die Etablierung einer C2C12-Zelllinie, welche ein EGFP-markiertes HMGA1a stabil exprimierte, konnte gezeigt werden, dass eine anhaltende HMGA1-Expression spezifisch die Myogeneseprozess inhibierte, w{\"a}hrend die Osteogenese davon unbeeinflusst zu bleiben schien. Dieser hemmende Effekt kann durch die HMGA1-abh{\"a}ngige Fehlexpression verschiedener Gene, welche f{\"u}r eine einwandfreie Muskeldifferenzierung n{\"o}tig sind und in die Zellzyklusregulation eingreifen, erkl{\"a}rt werden. Unter der Verwendung von RNAi konnte gezeigt werden, dass die Herunterregulierung von HMGA1-Proteinen f{\"u}r eine korrekte Genexpression und den Muskeldifferenzierungsprozess notwendig ist. W{\"a}hrend der terminalen Differenzierung wird die Umorganisation des Chromatins durch die Fusion der Chromozentren offensichtlich. Fotobleichtechniken, wie „fluorescence recovery after photobleaching" (FRAP) zeigten, dass HMGA1-Proteine mit dem Methyl-CpG-bindenden Protein 2 (MeCP2), welches eine wichtige Rolle in der Chromozentrenfusion spielt, um DNA-Bindungsstellen konkurriert und dieses vom Chromatin verdr{\"a}ngt. Diese dynamische Konkurrenz zwischen einem anhaltend exprimierten HMGA1 und MeCP2 tr{\"a}gt somit zur Inhibition der differenzierungsabh{\"a}ngigen Modulation des Chromatins w{\"a}hrend der sp{\"a}ten Myogenese bei. Die Untersuchungen in C2A1a-Zellen lieferten weitere Hinweise daf{\"u}r, dass der wesentlichste Umbau des Chromatins in einem Zeitfenster um den dritten Tag nach Induktion der Myogenese stattfindet, an welchem HMGA1 nat{\"u}rlicherweise nahezu vollst{\"a}ndig herunterreguliert sind. In diesem Zeitraum kommt es zur Dissoziation der Chromozentren, zu ver{\"a}nderten Expressionsmustern in bestimmten Genen, zu Modulationen in Histonmodifikationen (H3K4me2, H3K4me3, H3K27me3), zur Replikations-unabh{\"a}ngigen Akkumulation von Histon H3 in den Chromozentren {\"u}ber ungef{\"a}hr einen Zellzyklus hinweg und zu eine signifikanten Erh{\"o}hung der HP1-Dynamik. Durch den Einsatz von Bimolekularer Fluoreszenzkomplementierung (BiFC), die es erlaubt Protein-Protein-Interaktionen in vivo zu visualisieren, konnte gezeigt werden, dass der saure C-Terminus des HMGA mit der Chromodom{\"a}ne (CD) des HP1 interagiert. Zus{\"a}tzlich ist f{\"u}r diese Interaktion die korrekte DNA-Bindung des HMGA n{\"o}tig. FRAP-Messungen mit HP1-EGFP-Fusionsproteinen in Zellen die wildtypisches oder ein mutiertes HMGA koexprimierten, best{\"a}tigten diese Daten und wiesen darauf hin, dass die HP1-Verweildauer im Heterochromatin maßgeblich von der Gegenwart eines funktionellen HMGA1 abh{\"a}ngig ist. Des Weiteren zeigten C2C12-Myoblasten, die HMGA1 nat{\"u}rlicherweise exprimieren, eine hohe HP1-Verweildauer, die nach HMGA1-knock down drastisch verringert ist. Umgekehrt ist die HP1-Verweildauer nach einer Herunterregulierung von HMGA1 an Tag 3 der Myogenese gering und steigt durch die Koexpression von HMGA1 auf das in Myoblasten gemessene Niveau an. Zusammengenommen zeigen diese Daten, dass die differenzielle Expression von HMGA1 und ihre F{\"a}higkeit mit HP1 zu interagieren, sowie ihre Konkurrenz mit MeCP2 um DNA-Bindungsstellen einen entscheidende Rolle in der Regulation der Aufrechterhaltung und Plastizit{\"a}t des Heterochromatins w{\"a}hrend der Differenzierung spielen. Daher ist eine zeitlich festgelegte Herunterregulierung von HMGA1 notwendig, um die Modulation des Chromatins und dadurch den Differenzierungsprozess zu erm{\"o}glichen},
  subject      = {HMG-Proteine},
  language  = {de}
}