Histone methylation in Huntington's disease:are bivalent promoters the critical targets?

Huntington’s disease（HD）is a currently incurable,late onset,progressive,ultimately fatal neurological disorder（Bates et al.,2015）.We have recently published the results of comprehensive genetic interaction tests aimed at identification of histone methyltransferases and demethylases involved in HD pathogenesis in a Drosophila model of the disease（Song et al.,2018）.

Reducing intrathecal pressure after traumatic spinal cord injury: a potential clinical target to promote tissue survival

Spinal cord injury （SCI） is an unexpected event that is both devastating and debilitating, resulting in not just motor and sensory loss, but also autonomic dysfunction of the bladder, bowel and sexual organs. Currently, there are no treatments available to improve outcome follow- ing SCI, leaving individuals with permanent and lifelong physical disability. Worldwide it is estimated that more than 500,000 people sustain a SCI each year, with average lifetime cost of paraplegia and quadriplegia estimated at $5 million and $9.5 million respectively. We therefore urgently need effective therapies to improve quality of life following SCI, and this requires a greater understanding of how cell and axonal injury develops after the traumatic event.

Combined treatment promotes the long-range axon regeneration to right brain targets

Axons in the peripheral nervous system(PNS)can regenerate after injury.However,the adult mammalian central nervous system(CNS)loses the intrinsic regrowth ability.No robust axon regeneration occurs spontaneously after nerve injury,which was clearly observed by Ramon y Cajal in the early 20^(th) century(1,2).Due to lack

Many facades of CTCF unified by its coding for three-dimensional genome architecture

CCCTC-binding factor(CTCF)is a multifunctional zinc finger protein that is conserved in metazoan species.CTCF is consistently found to play an important role in many diverse biological processes.CTCF/cohesin-mediated active chromatin‘loop extrusion’architects three-dimensional(3D)genome folding.The 3D architectural role of CTCF underlies its multifarious functions,including developmental regulation of gene expression,protocadherin(Pcdh)promoter choice in the nervous system,immunoglobulin(Ig)and T-cell receptor(Tcr)V(D)J recombination in the immune system,homeobox(Hox)gene control during limb development,as well as many other aspects of biology.Here,we review the pleiotropic functions of CTCF from the perspective of its essential role in 3D genome architecture and topological promoter/enhancer selection.We envision the 3D genome as an enormous complex architecture,with tens of thousands of CTCF sites as connecting nodes and CTCF proteins as mysterious bonds that glue together genomic building parts with distinct articulation joints.In particular,we focus on the internal mechanisms by which CTCF controls higher order chromatin structures that manifest its many fa?ades of physiological and pathological functions.We also discuss the dichotomic role of CTCF sites as intriguing3D genome nodes for seemingly contradictory‘looping bridges’and‘topological insulators’to frame a beautiful magnificent house for a cell’s nuclear home.

The working dead:repurposing inactive CRISPR-associated nucleases as programmable transcriptional regulators in plants

Targeted gene manipulation is highly desirable for fundamental plant research,plant synthetic biology,and molecular breeding.The clustered regularly interspaced short palindromic repeats-associated(Cas)nuclease is a revolutionary tool for genome editing,and has received snowballing popularity for gene knockout applications in diverse organisms including plants.Recently,the nuclease-dead Cas(dCas)proteins have been repurposed as programmable transcriptional regulators through translational fusion with portable transcriptional repression or activation domains,which has paved new ways for flexible and multiplex control over the activities of target genes of interest without the need to generate DNA lesions.Here,we review the most important breakthroughs of dCas transcriptional regulators in non-plant organisms and recent accomplishments of this growing field in plants.We also provide perspectives on future development directions of dCas transcriptional regulators in plant research in hope to stimulate their quick evolution and broad applications.