Analysis of Development Edited by Prof Benjamin H Willier, Prof Paul A Weiss and Prof Viktor Hamburger Pp xii + 735 (Philadelphia and London: W B Saunders Company, 1955) 105s

Mechanisms of Development

Polycomb Group (PcG) proteins are crucial for epigenetic inheritance of cell identity and are functionally conserved from Drosophila to humans. PcG proteins regulate expression of homeotic genes and are essential for axial body patterning during development. Earlier we showed that transcription factor YY1 functions as a PcG protein. YY1 also physically interacts with YAF2, a homolog of RYBP. Here we characterize the mechanism and physiologic relevance of this interaction. We found phenotypic and biochemical correction of dRYBP mutant flies by mouse YAF2 demonstrating functional conservation across species. Further biochemical analysis revealed that YAF2 bridges interaction between YY1 and the PRC1 complex. ChIP assays in HeLa cells showed that YAF2 is responsible for PcG recruitment to DNA, which is mediated by YY1 DNA binding. Knock-down of YY1 abrogated PcG recruitment, which was not compensated by exogenous YAF2 demonstrating that YY1 DNA binding is a priori necessary for Polycomb assembly on chromatin. Finally, we found that although YAF2 and RYBP regulate a similar number of Polycomb target genes, there are very few genes that are regulated by both implying functional distinction between the two proteins. We present a model of YAF2-dependent and independent PcG DNA recruitment by YY1.

YY1 DNA binding and interaction with YAF2 is essential for Polycomb recruitment

INO80-dependent regression of ecdysone-induced transcriptional responses regulates developmental timing in Drosophila.

Background—Massively parallel, high-throughput sequencing technology is helping to generate new insights into the genetic basis of human diseases. We used whole exome sequencing to identify the mut...

Whole exome sequencing implicates an INO80D mutation in a syndrome of aortic hypoplasia, premature atherosclerosis, and arterial stiffness

The proper modulation of chromatin structure is dependent on the activities of chromatin-remodeling factors and their interplays. Here, we show that the Arabidopsis chromatin-remodeler AtINO80 interacts with the actin-related protein AtARP5 and can form a larger protein complex. Genetic analysis demonstrated that AtARP5 acts in concert with AtINO80 during plant cellular proliferation and replication stress response. At the same time, AtARP5 is not required for AtINO80-mediated control of flowering time and related transcriptional regulation, and their chromatin distribution patterns on regions of flowering-repressor genes FLC/MAF4/MAF5 are also different. An in vitro DNase I digestion assay revealed that the AtINO80N-terminus can weakly bind DNA, an interaction that is significantly inhibited by H2A.Z/H2B addition. AtARP6, a specific subunit of SWR1-C that mediates the H2A.Z exchange, was found to have a previously unexpected inhibitory role in the local chromatin enrichment of AtINO80. Further genetic analyses revealed the functional interplay between AtINO80 and AtARP6 and their critical roles in embryogenesis and post-embryonic organ development, as well as the synergy of AtARP5 and AtARP6 in maintaining genomic stability. Our findings provide insights into the common and distinct roles of AtINO80 and AtARP5 in diverse aspects of plant development.

https://nph.onlinelibrary.wiley.com/doi/epdf/10.1111/nph.15780

AtINO80 and AtARP5 physically interact and play common as well as distinct roles in regulating plant growth and development.

The homologues of yeast INO80 are identified across phyla from Caenorhabditis elegans to human. In Drosophila it has been shown that dINO80 forms a complex with Pleiohomeotic but does not interact with Hox PRE (polycomb responsive element). As some proteins of the INO80 complex are implicated in homeotic gene regulation, we examined if dINO80 is involved in regulation of homeotic genes. We find that dINO80 null mutants generated by imprecise excision of P-element are late embryonic lethals and show homeotic transformation. We detect misexpression of homeotic genes like Sex-comb reduced, Antennapedia, Ultrabithorax and Abdominal-B in dIno80 mutant embryos by immunostaining which is further substantiated by quantitative PCR. Polycomb phenotype in dIno80-Pc is enhanced in double mutants. Concurrently, the localization of dINO80 to sequences upstream of misexpressed genes in vivo shows that dINO80 is involved in homeotic gene regulation and probably through its interactions with PcG-trxG complexes.

Hema Pawar

Papers

Chromatin remodeling protein INO80 has a role in regulation of homeotic gene expression in Drosophila.

The functional diversity of Drosophila Ino80 in development