Targeting of the dosage-compensated male X-chromosome during early<i>Drosophila</i>development

Rieder, LE; Jordan, WT; Larschan, EN

doi:10.1101/671073

Cited by 5 publications

(6 citation statements)

References 49 publications

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“…In addition to GAF and Zld, the transcription factor CLAMP is expressed in the early embryo and functions in chromatin accessibility and transcriptional activation (Rieder et al 2017;Soruco et al 2013;Urban et al 2017aUrban et al , 2017bRieder et al 2019). While CLAMP, like GAF, binds GAdinucleotide repeats, the two proteins preferentially bind to slightly different GA-repeats (Kaye et al 2018).…”

Section: Maternally Encoded Gaf Is Essential For Development Beyond Tmentioning

confidence: 99%

GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo

Gaskill

Gibson

Larson

et al. 2021

eLife

101

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Following fertilization, the genomes of the germ cells are reprogrammed to form the totipotent embryo. Pioneer transcription factors are essential for remodeling the chromatin and driving the initial wave of zygotic gene expression. In Drosophila melanogaster, the pioneer factor Zelda is essential for development through this dramatic period of reprogramming, known as the maternal-to-zygotic transition (MZT). However, it was unknown whether additional pioneer factors were required for this transition. We identified an additional maternally encoded factor required for development through the MZT, GAGA Factor (GAF). GAF is necessary to activate widespread zygotic transcription and to remodel the chromatin accessibility landscape. We demonstrated that Zelda preferentially controls expression of the earliest transcribed genes, while genes expressed during widespread activation are predominantly dependent on GAF. Thus, progression through the MZT requires coordination of multiple pioneer-like factors, and we propose that as development proceeds control is gradually transferred from Zelda to GAF.

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Section: Maternally Encoded Gaf Is Essential For Development Beyond Tmentioning

confidence: 99%

GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo

Gaskill

Gibson

Larson

et al. 2021

eLife

101

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“…Sxl regulation of msl-2 RNA splicing and stability links the sex determination pathway to another important early embryonic event: dosage compensation, which equalizes gene dosage of X-linked genes between females with two X-chromosome and males with a single X-chromosome. MSL-2 is an essential core component of the MSL complex, present only in the male embryo and responsible for dosage compensation (Prayitno et al 2019; Rieder et al 2019). The binding of Sxl to the msl-2 transcript specifically in females results in skipping of the first exon in females, thereby hindering translation of the protein, which prevents MSL complex formation in females and allows it to be formed only in males (Gebauer et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Sex-specific transcript diversity is regulated by a maternal transcription factor in earlyDrosophilaembryos

Ray

Conard

Urban

et al. 2021

Preprint

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Maternally deposited RNAs and proteins play a crucial role in initiating zygotic transcription during early embryonic development. However, the mechanisms by which maternal factors regulate zygotic transcript diversity early in development remain poorly understood. Furthermore, how early in development sex-specific transcript diversity occurs is not known genome-wide in any organism. Here, we determine that sex-specific transcript diversity occurs much earlier in development than previously thought in Drosophila, concurrent with Zygotic genome activation (ZGA). We use genetic, biochemical, and genomic approaches to demonstrate that the essential maternally-deposited pioneer factor CLAMP (Chromatin linked adapter for MSL proteins) is a key regulator of sex-specific transcript diversity in the early embryo via the following mechanisms: 1) In both sexes, CLAMP directly binds to the gene bodies of female and male sex-specifically spliced genes. 2) In females, CLAMP modulates chromatin accessibility of an alternatively-spliced exon within Sex-lethal, the master regulator of sex determination, to promote protein production. 3) In males, CLAMP regulates Maleless (MLE) distribution, a spliceosome component to prevent aberrant sex-specific splicing. Thus, we demonstrate for the first time how a maternal factor regulates early zygotic transcriptome diversity sex-specifically. We also developed a new tool to measure how splicing changes over time called time2splice.

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“…Most HASs contain low-complexity GAGA motifs, referred to as the MRE (19,56). The CLAMP protein binds to MREs and is responsible for chromatin opening (28,92). Some C2H2 proteins that interact with MSL1 can functionally cooperate with CLAMP and bind to HASs.…”

Section: Discussionmentioning

confidence: 99%

“…This finding is in agreement with previous findings that the N-terminal 265 aa of MSL1, in cooperation with MSL2 and possibly with MLE, but not with MSL3 and MOF, can specifically bind to several sites on female polytene chromosomes (30). Rieder et al (92) showed that at the initiation of embryogenesis, the DCC first binds to all chromosomes before becoming concentrated on the X chromosome. Weak interactions with chromatin sites on autosomes likely lead to the rapid dissociation of the DCC, resulting in the gradual concentration of the DCC on HASs.…”

Section: Discussionmentioning

confidence: 99%

N-Terminus ofDrosophila MelanogasterMSL1 Is Critical for Dosage Compensation

Babosha

Klimenko

Tikhonova

et al. 2020

Preprint

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The male-specific lethal dosage compensation complex (MSL complex or DCC), which consists of five proteins and two non-coding roX RNAs, is necessary for the transcriptional enhancement of X-linked genes to compensate for the sex chromosome monosomy in Drosophila XY males, compared with XX females. MSL2 is a single protein component of the DCC that is expressed only in males and is essential for the specific recruitment of the DCC to the high-affinity “entry” sites (HASs) on the X chromosome. MSL2, together with MSL1, forms the heterotetrameric DCC core. Here, we demonstrated that the N-terminal unstructured region of MSL1 interacts with many different DNA-binding proteins that contain clusters of the C2H2 zinc-finger domains. Amino acid deletions in the N-terminal region of MSL1 strongly affect the binding of the DCC to the HASs on the male X chromosome. However, the binding of MSL2 to autosomal promoters was unaffected by amino acid deletions in MSL1. Males expressing mutant variants of MSL1 died during the larvae stage, demonstrating the critical role played by the N-terminal region in DCC activity. Our results suggest that MSL1 interacts with a variety of DNA-binding proteins to increase the specificity of DCC recruitment to the male X chromosome.BulletsThe N-terminal region of MSL1 interacts with 14 C2H2-type zinc-finger DNA-binding proteinsThe N-terminus of MSL1 is critical for the specific recruitment of the MSL complex to the X chromosomeThe N-terminus of MSL1 is important for the binding of MSL2 to a small fraction of autosomal promoters

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Targeting of the dosage-compensated male X-chromosome during earlyDrosophiladevelopment

Cited by 5 publications

References 49 publications

GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo

GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo

Sex-specific transcript diversity is regulated by a maternal transcription factor in earlyDrosophilaembryos

N-Terminus ofDrosophila MelanogasterMSL1 Is Critical for Dosage Compensation

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