• Distinct role of histone chaperone Asf1a and Asf1b during fertilization and pre-implantation embryonic development in mice. (omicsdi.org)
  • In such a crowded molecular picture, recent exciting insights have uncovered the role of histone variants as key regulators of the chromatin structure. (aging-us.com)
  • Although initially discovered as a retinoblastoma binding protein it has an affinity for core HISTONES and is a subunit of chromatin assembly factor-1 and polycomb repressive complex 2. (lookformedical.com)
  • Here, we identify mutants of histones H3.1 and H3.3 that are unable to interact with human ASF1A and ASF1B isoforms but that are still competent to bind CAF-1 and HIRA, respectively. (omicsdi.org)
  • We show that these mutant histones are inefficiently deposited into chromatin in vivo. (omicsdi.org)
  • Consistent with this, biochemical analysis of wild-type and phospho-mimetic Asf1a shows that phosphorylation enhances binding to histones and the downstream chaperones CAF-1 and HIRA. (omicsdi.org)
  • Moreover, we find that TLK phosphorylation of Asf1a is induced in cells experiencing deficiency of new histones and that TLK interaction with Asf1a involves its histone-binding pocket. (omicsdi.org)
  • We thus propose that TLK signalling promotes histone supply in S phase by targeting histone-free Asf1 and stimulating its ability to shuttle histones to sites of chromatin assembly. (omicsdi.org)
  • While canonical histones H3.1 and H3.2 are synthetized and loaded during DNA replication, the histone variant H3.3 is expressed and deposited into the chromatin throughout the cell cycle. (aging-us.com)
  • Among these regulatory processes, core and linker histones are subjected to a large pattern of posttranslational modifications (PTMs) that influence chromatin state and DNA accessibility [ 4 - 7 ]. (aging-us.com)
  • Along with PTMs, the partial or complete disassembly of nucleosomes allows the exchange and degradation of pre-existing histone proteins, with the incorporation of newly synthesised histones onto chromatin that can eventually result in the resetting of previous epigenetic marks. (aging-us.com)
  • A histone chaperone that facilitates nucleosome assembly by mediating the formation of the histone octamer and its transfer to DNA. (lookformedical.com)
  • Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly. (omicsdi.org)
  • Together, these studies begin to define the molecular determinants of assembly of functionally diverse macromolecular histone chaperone complexes. (omicsdi.org)
  • METHODS:We analyzed the dynamics of histone chaperone Asf1a and Asf1b in oocytes and pre-implantation embryos in mice by immunofluorescence and real-time quantitative PCR, and further investigated the role of Asf1a and Asf1b during fertilization and pre-implantation development by specific Morpholino oligos-mediated knock down approach. (omicsdi.org)
  • Furthermore, we found that both ASF1A and ASF1B participate in the DNA synthesis-independent deposition of H3.3 in HeLa cells, thus highlighting an unexpected role for ASF1B in this pathway. (omicsdi.org)
  • We provide the first direct determination that ASF1A and ASF1B play a role in the efficiency of nucleosome assembly in vivo in human cells. (omicsdi.org)
  • Human HIRA, ASF1a, ASF1b and CAF-1 are evolutionally conserved histone chaperones that form multiple functionally distinct chromatin-assembly complexes, with roles linked to diverse nuclear process, such as DNA replication and formation of heterochromatin in senescent cells. (omicsdi.org)
  • The N- and C-terminal regions of ASF1a and ASF1b determine the different affinities of these two proteins for HIRA, by contacting regions outside the HIRA B domain. (omicsdi.org)
  • Two paralogous genes, Asf1a and Asf1b exist in mammals, but their role during fertilization and early embryogenesis remains to be investigated further. (omicsdi.org)
  • RESULTS:Immunofluorescence with specific antibodies revealed that both Asf1a and Asf1b were deposited in the nuclei of fully grown oocytes, accumulated abundantly in zygote and 2-cell embryonic nuclei, but turned low at 4-cell stage embryos. (omicsdi.org)
  • In contrast to the weak but definite nuclear deposition of Asf1a, Asf1b disappeared from embryonic nuclei at morula and blastocyst stages. (omicsdi.org)
  • Eukaryotic cells compact their large genome into highly ordered chromatin structures within the nucleus. (aging-us.com)
  • A retinoblastoma-binding protein that is involved in CHROMATIN REMODELING, histone deacetylation, and repression of GENETIC TRANSCRIPTION. (lookformedical.com)
  • Consequently, H3.3 incorporation and turnover represent an additional layer in the regulation of the chromatin landscape during aging. (aging-us.com)
  • Incorporation of histone variants confers variability to the chromatin and expands the repertoire of epigenetic marks in a functional alphabet that controls genome plasticity and dynamics [ 4 ]. (aging-us.com)
  • The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA. (lookformedical.com)
  • The dynamic nature of chromatin establishes the access to the genetic material and, as a consequence, influences a large number of biological processes, such as DNA replication, repair and transcription [ 1 , 2 ]. (aging-us.com)
  • Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly. (nih.gov)
  • Histone chaperones have been implicated in nucleosome assembly and disassembly as well as histone modification. (omicsdi.org)
  • The protein is a key component of a histone donor complex that functions in nucleosome assembly. (nih.gov)
  • In vivo study of the nucleosome assembly functions of ASF1 histone chaperones in human cells. (omicsdi.org)
  • ASF1 is a highly conserved histone H3/H4 chaperone that synergizes in vitro with two other histone chaperones, chromatin assembly factor 1 (CAF-1) and histone repression A factor (HIRA), in DNA synthesis-coupled and DNA synthesis-independent nucleosome assembly. (omicsdi.org)
  • Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly. (omicsdi.org)
  • Human HIRA, ASF1a, ASF1b and CAF-1 are evolutionally conserved histone chaperones that form multiple functionally distinct chromatin-assembly complexes, with roles linked to diverse nuclear process, such as DNA replication and formation of heterochromatin in senescent cells. (omicsdi.org)
  • Together, these studies begin to define the molecular determinants of assembly of functionally diverse macromolecular histone chaperone complexes. (omicsdi.org)
  • Moreover, we find that TLK phosphorylation of Asf1a is induced in cells experiencing deficiency of new histones and that TLK interaction with Asf1a involves its histone-binding pocket. (omicsdi.org)
  • We thus propose that TLK signalling promotes histone supply in S phase by targeting histone-free Asf1 and stimulating its ability to shuttle histones to sites of chromatin assembly. (omicsdi.org)
  • Distinct role of histone chaperone Asf1a and Asf1b during fertilization and pre-implantation embryonic development in mice. (omicsdi.org)
  • METHODS:We analyzed the dynamics of histone chaperone Asf1a and Asf1b in oocytes and pre-implantation embryos in mice by immunofluorescence and real-time quantitative PCR, and further investigated the role of Asf1a and Asf1b during fertilization and pre-implantation development by specific Morpholino oligos-mediated knock down approach. (omicsdi.org)
  • Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly and with HIRA to promote replication-independent chromatin assembly. (nih.gov)
  • Here, we identify mutants of histones H3.1 and H3.3 that are unable to interact with human ASF1A and ASF1B isoforms but that are still competent to bind CAF-1 and HIRA, respectively. (omicsdi.org)
  • We report the crystal structure of an ASF1a-HIRA heterodimer and a biochemical dissection of ASF1a's mutually exclusive interactions with HIRA and the p60 subunit of CAF-1. (omicsdi.org)
  • The HIRA B domain forms an antiparallel beta-hairpin that binds perpendicular to the strands of the beta-sandwich of ASF1a, via beta-sheet, salt bridge and van der Waals contacts. (omicsdi.org)
  • The N- and C-terminal regions of ASF1a and ASF1b determine the different affinities of these two proteins for HIRA, by contacting regions outside the HIRA B domain. (omicsdi.org)
  • CAF-1 p60 also uses B domain-like motifs for binding to ASF1a, thereby competing with HIRA. (omicsdi.org)
  • Consistent with this, biochemical analysis of wild-type and phospho-mimetic Asf1a shows that phosphorylation enhances binding to histones and the downstream chaperones CAF-1 and HIRA. (omicsdi.org)
  • Furthermore, we found that both ASF1A and ASF1B participate in the DNA synthesis-independent deposition of H3.3 in HeLa cells, thus highlighting an unexpected role for ASF1B in this pathway. (omicsdi.org)
  • In contrast to the weak but definite nuclear deposition of Asf1a, Asf1b disappeared from embryonic nuclei at morula and blastocyst stages. (omicsdi.org)