Friday 26 May 2017

Embroygensis

Cited from the paper Embryonic stem cell potency fluctuates with endogenous retrovirus activity

The zygote and its daughter cells are totipotent because they are able to develop into all embryonic and extraembryonic cell types. The progeny of these first two daughter cells become progressively more fate-restricted as they activate distinct patterns of gene expression that first direct them towards one of three broad lineages: Oct4+ Sox2+ Nanog+ epiblast cells that give rise to the embryo, Gata4+/6+ primitive endoderm cells that contribute to extraembryonic membranes that encase the embryo, and Cdx2+ trophectoderm cells that form a large part of the placenta.

Friday 19 May 2017

Superenhancers

Most cell types are found to have 300–500 super-enhancers.

Mediator and Cohesin

Cited from the paper The selection and function of cell type-specific enhancers

Through looping of the intervening DNA, enhancers are brought into close proximity of promoters and are thought to affect any or all of the aforementioned processes by increasing the local concentrations of the factors involved. These factors include co-activator complexes such as the Mediator complex, which increases the loading of transcription factors onto promoters and enhancers; scaffold proteins, such as cohesin, that mediate stable and often cell type-specific promoter–enhancer interactions; and factors that are involved in releasing paused Pol II and in the initiation of elongation, such as BRD4.
Cohesin and the Mediator complex are scaffold proteins of the replication machinery and the transcription machinery, respectively.
Cohesin seems to be recruited to enhancers through clusters of lineage-determining transcription factors (LDTFs).

Thursday 18 May 2017

Enhancer States

Cited from The selection and function of cell type-specific enhancers

  1. Enhancer states can broadly be classified as inactive, primed, poised or active. 
  2. An inactive enhancer is essentially buried in compact chromatin and is devoid of transcription factor binding and histone modifications. 
  3. Primed enhancers are characterized by closely bound sequence-specific transcription factors that establish a DNase I-hypersensitive and nucleosome-free region of open chromatin.
  4. However, they may require additional cues to accomplish their function, which may include signal-dependent activation, the recruitment of additional transcription factors and the eventual recruitment of co-activators that lead to enhancer activation.
  5. Poised enhancers can be defined as primed enhancers that also contain repressive epigenetic chromatin marks, a state that is most commonly found in ESCs.
  6. The redundant histone methyltransferases myeloid/lymphoid or mixed-lineage leukaemia protein 3 (MLL3) and MLL4 deposit the active histone H3 lysine 4 monomethylation (H3K4me1) and H3K4me2 marks.
  7. At poised enhancers, the histone-lysine N-methyltransferase EZH2 (a component of the Polycomb complex) deposits repressive H3K27me3 marks, and histone deacetylase (HDAC)-containing complexes maintain histones in a repressed, deacetylated state.
  8. RNA polymerase II (Pol II) is either absent or found at low levels at poised enhancers.
  9. In response to various cues, signal-dependent transcription factors (SDTFs) associate with recognition motifs in close association with LDTFs, which results in additional nucleosome displacement, as observed by widening of the DNase I-hypersensitive sites.
  10. SDTFs recruit co-activator complexes containing histone demethylase (HDM) complexes that remove H3K27me3 marks, histone acetyltransferases (HATs) that deposit H3K27 acetylation (H3K27ac) marks, and the Mediator complex (MED).
  11. Primed enhancer-like regions are marked with H3K4me1 and H3K4me2 and lack histone acetylation, and enhancers marked additionally by H3K27me3, a repressive mark, are considered to be poised. 
  12. Features associated with active enhancers include H3K27 acetylation (H3K27ac) and the presence of actively transcribing Pol II. 
  13. Lineage-determining transcription factors (LDTF) motif composition may be one of the contributing factors to the formation of transcriptionally inactive and active genomic compartments. 
  14. ChIP–seq studies of signal-dependent transcription factors (SDTFs) in different cell types found both common and cell type-specific binding sites.
  15. Of note, the histone methylation signature of latent enhancers persists after the cessation of cell stimulation and is associated with more-rapid and more-diverse transcriptional responses to subsequent stimulation. These observations provide evidence that the writing of the H3K4me1 signature in enhancers provides a molecular 'memory' of prior activation.

What Is Metazoan?

Cited from merriam-webste

Metazoan: any of a group (Metazoa) that comprises all animals having the body composed of cells differentiated into tissues and organs and usually a digestive cavity lined with specialized cells.

Differentiation of H3K4me2 from H3K4me3


Both H3K4me2 and H3K4me3 are found predominantly on active loci, although H3K4me3 occurs concomitantly with active transcription, while H3K4me2 can be present on poised, inactive genes.
Usually, H3K4me2 and H3K4me3 both peak at the transcription start site. Recent evidence suggests that H3K4me3 occurs after the general transcription machinery assembles on the promoter.

Merge Multiple PDFs (Including Encrypted PDFs) in Linux

Cited from How do you merge protected PDF files?

gs -dBATCH -dNOPAUSE -q -sDEVICE=pdfwrite -sOutputFile=Reimbursement.pdf Payment_Req_Form_sign.pdf MeetingAgenda.pdf Approval.pdf FoodOrder.pdf BankStatement.pdf

Friday 12 May 2017

R Packages: Organize, Test, Document, and Share Your Code

R packages

R Parser

Cited from the book "Extending R"

The parser’s job is simply to convert the text into an object that represents R’s interpretation of what you typed.

R Namespace

Cited from the book "Extending R"

Once a package has been loaded into the R process, the corresponding namespace is an object (an "environment") containing all the objects from that package

To extract the namespace of a package

ns <- asNamespace([package name])

Use str(ns$'function name') to see the structure of a named function within a package.

Thursday 11 May 2017

R S4 Programming Check Validity

Once an S4 class is defined (using "setClass"), sanity checks can be re-enforced by defining "setValidity" function.

Equivalently, you can also specify "validity" method as an argument to the "setClass" function.

You can check a class object is valid using "validObject" function.




Underused R Functions

missing’ can be used to test whether a value was specified as an argument to a function.

"existsMethod" seeks methods for the current class, but "hasMethod" seeks methods for the current class and parental classes.

Likewise, "getMethod" and "selectMethod" have respective behaviour with inheritance.