Biology subjects

Meller, V. H.

Publications and source records attributed to Meller, V. H..

2 recordsLinked to original sources

bioRxiv2024

Drosophila melanogaster employs nuclear architecture for recruitment of dosage compensation

Drosophila melanogaster males increase expression from their single X chromosome to match the expression from two female X chromosomes. Increased expression involves recruitment of the Male Specific Lethal (MSL) complex to X-linked genes and modification of chromatin by this complex. How X-linked genes are selectively identified remains unclear, but cis-acting recruiting elements are involved. Chromatin Entry Sites (CES) bind an adapter protein that directly recruits the MSL complex. In addition, a class of AT-rich satellites, the 1.688X repeats, are enriched on the X and facilitate compensation of nearby genes. How these elements cooperate to identify the X is unknown. Nuclear architecture influences dosage compensation in many organisms. In this study we test the idea that factors involved in nuclear architecture participate in recruitment by the CES and 1.688X repeats. We find genetic interactions between mutations that reduce X recognition and factors that govern chromatin structure, silencing, remodeling and insulation, suggesting roles in X recognition. A reporter for recruitment revealed that Heterochromatin Protein 2 (HP2) and Scaffold Attachment Factor-A (SAF-A) disrupt compensation but do not selectively influence recruitment by either element. In contrast, Imitation switch (ISWI), D1 and Nucleoporin 153kD (Nup153) contribute to recruitment by the CES and Centrosomal protein 190kD (Cp190) exerts a striking influence on recruitment by 1.688X repeats. These findings reveal that recruitment by the CES and 1.688X repeats involves nuclear organization. We propose that the use of cis-acting elements that engage complementary aspects of nuclear organization ensures robust X recognition.

genetics↗

bioRxiv2018

Chromatin at X-linked repeats that guide dosage compensation in Drosophila melanogaster is modulated by the siRNA pathway

Many heterogametic organisms adjust sex chromosome expression to accommodate differences in gene dosage. This requires selective recruitment of regulatory factors to the modulated chromosome. How these factors are localized to a chromosome with requisite accuracy is poorly understood. Drosophila melanogaster males increase expression from their single X chromosome. Identification of this chromosome involves cooperation between different classes of X-identity elements. The Chromatin Entry Sites (CES) recruit a chromatin-modifying complex that spreads into nearby genes and increases expression. In addition, a family of satellite repeats that is enriched on the X chromosome, the 1.688X repeats, promotes recruitment of the complex to nearby genes. The 1.688X repeats and CES are dissimilar, and appear to operate through different mechanisms. Interestingly, the siRNA pathway and siRNA from a 1.688X repeat also promote X recognition. We postulate that siRNA-dependent modification of 1.688X chromatin contributes to recognition of nearby genes. In accord with this, we found enrichment of the siRNA effector Argonaute2 (Ago2) at some 1.688X repeats.Mutations in several proteins that physically interact with Ago2, including the histone methyltransferase Su(var)3-9, enhance the lethality of males with defective X recognition. Su(var)3-9 deposits H3K9me2 on some 1.688X repeats, and this mark is disrupted upon ectopic expression of 1.688X siRNA. Furthermore, integration of 1.688X DNA on an autosome induces local H3K9me2 deposition, but enhances expression of nearby genes in a siRNA-dependent manner. Our findings are consistent with a model in which siRNA-directed modification of 1.688X chromatin contributes to recognition of the fly X chromosome by the MSL complex.

genetics↗