A5072081531- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- Animal Genetics and Reproduction
- Advanced biosensing and bioanalysis techniques
- Cancer-related molecular mechanisms research
- Prenatal Screening and Diagnostics
- Ovarian function and disorders
- Ubiquitin and proteasome pathways
- Pluripotent Stem Cells Research
- Histone Deacetylase Inhibitors Research
- Renal and related cancers
- Fungal and yeast genetics research
University of Pennsylvania
2015-2024
California University of Pennsylvania
2024
Capital Normal University
2023-2024
University of California, Los Angeles
2023
Wuhan University
2023
Nanjing Medical University
2018
Philadelphia University
2014
Massachusetts Institute of Technology
2001
Howard Hughes Medical Institute
2001
The N6-methyladenosine (m6A) modification is the most prevalent internal RNA in eukaryotes. majority of m6A sites are found last exon and 3' UTRs. Here we show that nuclear reader YTHDC1 essential for embryo viability germline development mouse. Specifically, required spermatogonial males oocyte growth maturation females; Ythdc1-deficient oocytes blocked at primary follicle stage. Strikingly, loss leads to extensive alternative polyadenylation oocytes, altering UTR length. Furthermore,...
During meiosis, the arrangement of homologous chromosomes is tightly regulated by synaptonemal complex (SC). Each SC consists two axial/lateral elements (AEs/LEs), and numerous transverse filaments. protein 2 (SYCP2) SYCP3 are integral components AEs/LEs in mammals. We find that SYCP2 forms heterodimers with both vitro vivo. An evolutionarily conserved coiled coil domain required for binding to SYCP3. generated a mutant Sycp2 allele mice lacks domain. The fertility homozygous sexually...
Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, form chiasmata. The homologues connect via axial elements numerous transverse filaments synaptonemal complex. complex a critical component chromosome pairing, segregation, recombination. We previously identified novel cell–specific HORMA domain encoding gene, Hormad1, member of mammalian counterpart yeast protein Hop1. Hormad1 gametogenesis as knockout...
Research Article1 July 2015Open Access TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates mouse Fang Yang Department of Biomedical Sciences, School Veterinary Medicine, University Pennsylvania, Philadelphia, PA, USA Search for more papers by this author Sherman Silber Infertility Center St. Louis, Luke's Hospital, MO, N Adrian Leu Robert D Oates Urology, Boston Medical Center, Boston, MA, Janet Marszalek Howard Hughes Institute, Whitehead...
Piwi–piRNA (Piwi-interacting RNA) ribonucleoproteins (piRNPs) enforce retrotransposon silencing, a function critical for preserving the genome integrity of germ cells. The molecular functions most factors that have been genetically implicated in primary piRNA biogenesis are still elusive. Here we show MOV10L1 exhibits 5′-to-3′ directional RNA-unwinding activity vitro and point mutation abolishes this causes failure vivo. We demonstrate selectively binds precursor transcripts is essential...
Piwi-interacting RNAs are a diverse class of small non-coding implicated in the silencing transposable elements and safeguarding genome integrity. In mammals, male germ cells express two genetically developmentally distinct populations piRNAs at pre-pachytene pachytene stages meiosis, respectively. Pre-pachytene mostly derived from retrotransposons required for their silencing. contrast, originate ∼3,000 genomic clusters, biogenesis function remain enigmatic. Here, we report that conditional...
We have examined expression during spermatogenesis in the mouse of three Y-linked genes, 11 X-linked genes and 22 autosomal all previously shown to be germ-cell-specific expressed premeiotic spermatogonia, plus another 21 that initiate meiotic spermatocytes. Our data demonstrate that, like sex-linked housekeeping are subject sex-chromosome inactivation (MSCI). Although we investigated underwent MSCI, 14 spermatogonia showed no decrease This along with our observation an additional or...
Nuages are found in the germ cells of diverse organisms. However, nuages postnatal male mice poorly studied. Previously, we cloned a cell-specific gene named Rnf17, which encodes protein containing both RING finger and tudor domains. Here, report that RNF17 is component novel nuage - granule, an electron-dense non-membrane bound spherical organelle with diameter 0.5 μm. granules prominent late pachytene diplotene spermatocytes, elongating spermatids. distinguishable from other known nuages,...
During spermiogenesis, haploid round spermatids undergo dramatic cell differentiation and morphogenesis to give rise mature spermatozoa for fertilization, including nuclear elongation, chromatin remodeling, acrosome formation, development of flagella. The molecular mechanisms underlining these fundamental processes remain poorly understood. Here, we report that MNS1, a coiled-coil protein unknown function, is essential spermiogenesis. We find MNS1 expressed in the germ cells testes localizes...
Significance TATA-binding protein (TBP)-associated factor 7l ( Taf7l ), Taf4b , and TBP-related 2 Trf2 ) were found to be three important atypical testis-specific core promoter recognition factors. However, whether there was any functional cross-talk between them at which stages of spermatogenesis remained uncharacterized. Here we report that − /Y becomes sterile rather than merely subfertile after backcrossing. Importantly, cooperates with but not late direct the transcription key...
Meiotic recombination permits exchange of genetic material between homologous chromosomes. The replication protein A (RPA) complex, the predominant ssDNA-binding is required for nearly all aspects DNA metabolism, but its role in mammalian meiotic remains unknown due to embryonic lethality RPA mutant mice. a heterotrimer RPA1, RPA2, and RPA3. We find that loss largest subunit, leads disappearance RPA2 RPA3, resulting absence complex. Using an inducible germline-specific inactivation strategy,...
Polycomb group proteins mediate transcriptional silencing in diverse developmental processes. Sex chromosomes undergo chromosome-wide transcription during male meiosis. Here we report that mouse SCML2 (Sex comb on midleg-like 2), an X chromosome-encoded polycomb protein, is specifically expressed germ cells, including spermatogonia, spermatocytes, and round spermatids. associates with phosphorylated H2AX localizes to the XY body spermatocytes. Loss of mice causes defective spermatogenesis,...
SKP1 coordinates chromosome synapsis and meiotic recombination with progression through the first cell division in mouse.
Abstract Breast cancer susceptibility gene II ( BRCA2 ) is central in homologous recombination (HR). In meiosis, binds to MEILB2 localize DNA double-strand breaks (DSBs). Here, we identify and MEILB2-associating protein 1 (BRME1), which functions as a stabilizer of by binding an α-helical N-terminus preventing self-association. the C-terminus MEILB2, resulting formation BRCA2-MEILB2-BRME1 ternary complex. Brme1 knockout −/− mice, BRCA2-MEILB2 complex destabilized, leading defects DSB repair,...
The transition from meiotic spermatocytes to postmeiotic haploid germ cells constitutes an essential step in spermatogenesis. epigenomic regulatory mechanisms underlying this remain unclear. Here, we find a prominent transcriptomic switch the late early round spermatids during meiotic-to-postmeiotic transition, which is associated with robust histone acetylation changes across genome. Among deacetylases (HDACs) and acetyltransferases, that HDAC3 selectively expressed stages. Three...
Self-renewal of spermatogonial stem cells is vital to lifelong production male gametes and thus fertility. However, the underlying mechanisms remain enigmatic. Here, we show that DOT1L, sole H3K79 methyltransferase, required for cell self-renewal. Mice lacking DOT1L fail maintain cells, characterized by a sequential loss germ from spermatogonia spermatids ultimately Sertoli only syndrome. Inhibition reduces activity after transplantation. promotes expression fate-determining HoxC...
Meiotic recombination ensures faithful segregation of homologous chromosomes during meiosis and generates genetic diversity in gametes. MEIOB (meiosis specific with OB domains), a meiosis-specific single-stranded DNA-binding homolog replication protein A1 (RPA1), is essential for meiotic recombination. Here, we investigated the molecular mechanisms by characterizing its binding partners spermatogenesis associated 22 (SPATA22) RPA. We find that SPATA22 form an obligate complex contain defined...
Abstract Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role SKP1, a constitutive subunit the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early processes. SKP1 restrains accumulation HORMAD1 pre-DSB complex (IHO1-REC114-MEI4) on chromosome axis germ cells. Loss prior to meiosis leads aberrant localization DSB repair proteins failure synapsis initiation both males females....