PARP-1 Flips the Epigenetic Switch on Obesity.

PARP enzymes are increasingly taking on important roles beyond DNA repair. Huang et al. (2020b) report how the NAD+-dependent ADP-ribosylation of histone H2B by PARP-1 in complex with a metabolic enzyme suppresses the phosphorylation of an adjacent residue, impacting adipogenesis.

The Role of Mammalian Creb3-Like Transcription Factors in Response to Nutrients.

Our ability to overcome the challenges behind metabolic disorders will require a detailed understanding of the regulation of responses to nutrition. The Creb3 transcription factor family appears to have a unique regulatory role that links cellular secretory capacity with development, nutritional state, infection, and other stresses. This role in regulating individual secretory capacity genes could place this family of transcription factors at an important regulatory intersection mediating an animal's responses to nutrients and other environmental challenges. Interestingly, in both humans and mice, individuals with mutations in Creb3L3/CrebH, one of the Creb3 family members, exhibit hypertriglyceridemia (HTG) thus linking this transcription factor to lipid metabolism. We are beginning to understand how Creb3L3 and related family members are regulated and to dissect the potential redundancy and cross talk between distinct family members, thereby mediating both healthy and pathological responses to the environment. Here, we review the current knowledge on the regulation of Creb3 family transcription factor activity, their target genes, and their role in metabolic disease.

Designing Cell-Type-Specific Genome-wide Experiments.

Multicellular organisms depend on cell-type-specific division of labor for survival. Specific cell types have their unique developmental program and respond differently to environmental challenges, yet are orchestrated by the same genetic blueprint. A key challenge in biology is thus to understand how genes are expressed in the right place, at the right time, and to the right level. Further, this exquisite control of gene expression is perturbed in many diseases. As a consequence, coordinated physiological responses to the environment are compromised. Recently, innovative tools have been developed that are able to capture genome-wide gene expression using cell-type-specific approaches. These novel techniques allow us to understand gene regulation in vivo with unprecedented resolution and give us mechanistic insights into how multicellular organisms adapt to changing environments. In this article, we discuss the considerations needed when designing your own cell-type-specific experiment from the isolation of your starting material through selecting the appropriate controls and validating the data.

CAST-ChIP maps cell-type-specific chromatin states in the Drosophila central nervous system.

Chromatin organization and gene activity are responsive to developmental and environmental cues. Although many genes are transcribed throughout development and across cell types, much of gene regulation is highly cell-type specific. To readily track chromatin features at the resolution of cell types within complex tissues, we developed and validated chromatin affinity purification from specific cell types by chromatin immunoprecipitation (CAST-ChIP), a broadly applicable biochemical procedure. RNA polymerase II (Pol II) CAST-ChIP identifies ~1,500 neuronal and glia-specific genes in differentiated cells within the adult Drosophila brain. In contrast, the histone H2A.Z is distributed similarly across cell types and throughout development, marking cell-type-invariant Pol II-bound regions. Our study identifies H2A.Z as an active chromatin signature that is refractory to changes across cell fates. Thus, CAST-ChIP powerfully identifies cell-type-specific as well as cell-type-invariant chromatin states, enabling the systematic dissection of chromatin structure and gene regulation within complex tissues such as the brain.