Parallel evolution of male germline epigenetic poising and somatic development in animals.
Nature Genetics 48(8):888 (2016)
Changes in gene regulation frequently underlie changes in morphology during evolution, and differences in chromatin state have been linked with changes in anatomical structure and gene expression across evolutionary time. Here we assess the relationship between evolution of chromatin state in ge...
The history of the Y chromosome in man.
Nature Genetics 48(6):588 (2016)
Studies of the Y chromosome over the past few decades have opened a window into the history of our species, through the reconstruction and exploitation of a patrilineal (Y-genealogical) tree based on several hundred single-nucleotide variants (SNVs). A new study validates, refines and extends th...
A mitotic SKAP isoform regulates spindle positioning at astral microtubule plus ends.
Journal of Cell Biology 213(3):315 (2016)
The Astrin/SKAP complex plays important roles in mitotic chromosome alignment and centrosome integrity, but previous work found conflicting results for SKAP function. Here, we demonstrate that SKAP is expressed as two distinct isoforms in mammals: a longer, testis-specific isoform that was used ...
Developing a utility decision framework to evaluate predictive models in breast cancer risk estimation.
Journal of medical imaging (Bellingham, Wash.) 2(4):041005 (2015)
Combining imaging and genetic information to predict disease presence and progression is being codified into an emerging discipline called "radiogenomics." Optimal evaluation methodologies for radiogenomics have not been well established. We aim to develop a decision framework based on utility a...
TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse.
Embo Molecular Medicine 7(9):1198 (2015)
Genome-wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11, an X-linked meiosis-specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX11 is mutated in infertile men with non-obstructive azoospermia and that an ana...
Proceedings from the Turner Resource Network symposium: the crossroads of health care research and health care delivery.
American Journal of Medical Genetics Part A 167A(9):1962 (2015)
Turner syndrome, a congenital condition that affects ∼1/2,500 births, results from absence or structural alteration of the second sex chromosome. There has been substantial effort by numerous clinical and genetic research groups to delineate the clinical, pathophysiological, cytogenetic, and mol...
A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary.
PLoS Genetics 11(9):e1005531 (2015)
The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, p...
Periodic retinoic acid-STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis.
PNAS 112(18):E2347 (2015)
Mammalian spermatogenesis--the transformation of stem cells into millions of haploid spermatozoa--is elaborately organized in time and space. We explored the underlying regulatory mechanisms by genetically and chemically perturbing spermatogenesis in vivo, focusing on spermatogonial differentiat...
Licensing of primordial germ cells for gametogenesis depends on genital ridge signaling.
PLoS Genetics 11(3):e1005019 (2015)
In mouse embryos at mid-gestation, primordial germ cells (PGCs) undergo licensing to become gametogenesis-competent cells (GCCs), gaining the capacity for meiotic initiation and sexual differentiation. GCCs then initiate either oogenesis or spermatogenesis in response to gonadal cues. Germ cell ...
Sex chromosome-to-autosome transposition events counter Y-chromosome gene loss in mammals.
Genome Biology 16(1):104 (2015)
Although the mammalian X and Y chromosomes evolved from a single pair of autosomes, they are highly differentiated: the Y chromosome is dramatically smaller than the X and has lost most of its genes. The surviving genes are a specialized set with extraordinary evolutionary longevity. Most mammal...
The Biology and Evolution of Mammalian Y Chromosomes.
Genetics 49:507 (2015)
Mammals have the oldest sex chromosome system known: the mammalian X and Y chromosomes evolved from ordinary autosomes beginning at least 180 million years ago. Despite their shared ancestry, mammalian Y chromosomes display enormous variation among species in size, gene content, and structural c...
The E2 ubiquitin-conjugating enzyme UBE2J1 is required for spermiogenesis in mice.
Journal of Biological Chemistry 289(50):34490 (2014)
ER-resident proteins destined for degradation are dislocated into the cytosol by components of the ER quality control machinery for proteasomal degradation. Dislocation substrates are ubiquitylated in the cytosol by E2 ubiquitin-conjugating/E3 ligase complexes. UBE2J1 is one of the well-characte...
Excess cholesterol induces mouse egg activation and may cause female infertility.
PNAS 111(46):E4972 (2014)
The HDL receptor scavenger receptor, class B type I (SR-BI) controls the structure and fate of plasma HDL. Female SR-BI KO mice are infertile, apparently because of their abnormal cholesterol-enriched HDL particles. We examined the growth and meiotic progression of SR-BI KO oocytes and found tha...
Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes.
Cell 159(4):800 (2014)
We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene poor, the mouse MSY is 99.9% euchromatic and contains about 700 protein-coding genes. Only 2% of th...
Poised chromatin in the mammalian germ line.
Development 141(19):3619 (2014)
Poised (bivalent) chromatin is defined by the simultaneous presence of histone modifications associated with both gene activation and repression. This epigenetic feature was first observed at promoters of lineage-specific regulatory genes in embryonic stem cells in culture. More recent work has ...
Retinoic acid activates two pathways required for meiosis in mice.
PLoS Genetics 10(8):e1004541 (2014)
In all sexually reproducing organisms, cells of the germ line must transition from mitosis to meiosis. In mice, retinoic acid (RA), the extrinsic signal for meiotic initiation, activates transcription of Stra8, which is required for meiotic DNA replication and the subsequent processes of meiotic...
A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response.
Cell 157(4):869 (2014)
Fragile X syndrome, a common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein FMRP. FMRP is present predominantly in the cytoplasm, where it regulates translation of proteins that are important for synaptic function. We identify FMRP as a c...
Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators.
Nature 508(7497):494 (2014)
The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene ...
No bull: upholding community standards in public sharing of biological datasets.
PNAS 110(46):E4277 (2013)
A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis.
PNAS 110(40):16061 (2013)
In multicellular organisms, germ cells carry the hereditary material from one generation to the next. Developing germ cells are unipotent gamete precursors, and mature gametes are highly differentiated, specialized cells. However, upon gamete union at fertilization, their genomes drive a totipot...