TY - JOUR

T1 - Impact of Xist RNA on chromatin modifications and transcriptional silencing maintenance at different stages of imprinted X chromosome inactivation in vole Microtus levis

AU - Shevchenko, Alexander I.

AU - Grigor’eva, Elena V.

AU - Medvedev, Sergey P.

AU - Zakharova, Irina S.

AU - Dementyeva, Elena V.

AU - Elisaphenko, Eugeny A.

AU - Malakhova, Anastasia A.

AU - Pavlova, Sophia V.

AU - Zakian, Suren M.

N1 - Publisher Copyright: © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - In vole Microtus levis, cells of preimplantation embryo and extraembryonic tissues undergo imprinted X chromosome inactivation (iXCI) which is triggered by a long non-coding nuclear RNA, Xist. At early stages of iXCI, chromatin of vole inactive X chromosome is enriched with the HP1 heterochromatin-specific protein, trimethylated H3K9 and H4K20 attributable to constitutive heterochromatin. In the study, using vole trophoblast stem (TS) cells as a model of iXCI, we further investigated chromatin of the inactive X chromosome of M. levis and tried to find out the role of Xist RNA. We demonstrated that chromatin of the inactive X chromosome in vole TS cells also contained the SETDB1 histone methyltransferase and KAP1 protein. In addition, we observed that Xist RNA did not contribute significantly to maintenance of X chromosome inactive state during iXCI in vole TS cells. Xist repression affected neither transcriptional silencing caused by iXCI nor maintenance of trimethylated H3K9 and H4K20 as well as HP1, KAP1, and SETDB1 on the inactive X chromosome. Moreover, the unique repertoire of chromatin modifications on the inactive X chromosome in vole TS cells could be disrupted by a chemical compound, DZNep, and then restored even in the absence of Xist RNA. However, Xist transcript was necessary for recruitment of an additional repressive histone modification, trimethylated H3K27, to the inactive X chromosome during vole TS cell differentiation.

AB - In vole Microtus levis, cells of preimplantation embryo and extraembryonic tissues undergo imprinted X chromosome inactivation (iXCI) which is triggered by a long non-coding nuclear RNA, Xist. At early stages of iXCI, chromatin of vole inactive X chromosome is enriched with the HP1 heterochromatin-specific protein, trimethylated H3K9 and H4K20 attributable to constitutive heterochromatin. In the study, using vole trophoblast stem (TS) cells as a model of iXCI, we further investigated chromatin of the inactive X chromosome of M. levis and tried to find out the role of Xist RNA. We demonstrated that chromatin of the inactive X chromosome in vole TS cells also contained the SETDB1 histone methyltransferase and KAP1 protein. In addition, we observed that Xist RNA did not contribute significantly to maintenance of X chromosome inactive state during iXCI in vole TS cells. Xist repression affected neither transcriptional silencing caused by iXCI nor maintenance of trimethylated H3K9 and H4K20 as well as HP1, KAP1, and SETDB1 on the inactive X chromosome. Moreover, the unique repertoire of chromatin modifications on the inactive X chromosome in vole TS cells could be disrupted by a chemical compound, DZNep, and then restored even in the absence of Xist RNA. However, Xist transcript was necessary for recruitment of an additional repressive histone modification, trimethylated H3K27, to the inactive X chromosome during vole TS cell differentiation.

KW - Histone modifications

KW - Imprinted X chromosome inactivation

KW - Vole

KW - Xist

KW - CELLS

KW - MOUSE

KW - GENOME

KW - FACULTATIVE HETEROCHROMATIN

KW - COMMON VOLES

KW - SEQUENCE

KW - MICE

KW - EXPRESSION

KW - GENUS MICROTUS

KW - MAMMALS

UR - http://www.scopus.com/inward/record.url?scp=85034273524&partnerID=8YFLogxK

U2 - 10.1007/s00412-017-0650-9

DO - 10.1007/s00412-017-0650-9

M3 - Article

C2 - 29151149

AN - SCOPUS:85034273524

VL - 127

SP - 129

EP - 139

JO - Chromosoma

JF - Chromosoma

SN - 0009-5915

IS - 1

ER -