Gen CH 15
The NFR is flanked by two-well positioned nucleosomes that are termed the _____. These may contain histone variants that are important in regulation of transcription.
-1 and +1 nucleosomes
Enhancers typically they increase activity _____ fold
1,000 to 10,000
There are three basic mechanisms of regulating transcription factor function
1. The binding of an effector molecule 2. Protein-protein interactions 3. Covalent modification of the transcription factor
In mammals, _____ of the DNA is methylated
2-7%
The ferritin mRNA has an IRE in an untranslated region, between the _____. When iron levels are low, IRP binds to this IRE and translation is blocked
5' end and the start codon
One key discovery that more than _____ of the DNA in the human genome has a biological function
80%
_____ allows for the determination of where nucleosomes are located, where histone variants are found, and where covalent modifications of histones occur
Chromatin immunoprecipitation sequencing (ChIP-Seq)
A sequence of DNA (or RNA) that binds a regulatory protein and thereby influences gene expressions. Bacterial operator sites and eukaryotic enhancers and silencers are examples
Control elements, regulatory elements, or regulatory sequences
_____ are sites of methylation and gene regulation.
CpG islands
_____ is a mechanism that silences gene expression
DNA methylation
All remodeling complexes have a catalytic ATPase subunit in a complex that is called a _____, which moves along the DNA. These proteins are similar to motor proteins.
DNA translocase
_____ are regions of transcription factors that have specific functions. A domain that has a similar structure in many different proteins is called a _____
Domains, motif
The central goal of _____ is to build a comprehensive list of functional elements in the human genome
ENCODE
_____ DNA has both strands methylated
Fully methylated
Each of the core histone proteins consists of a _____ and a felxible, charged amino-terminus called an _____
Globular domain, amino-terminal tail
_____ hormones influence nutrient metabolism in most body cells
Glucocorticoid
Isolation and sequencing of RNA molecules transcribed from the human genome. Identification of DNA binding sites for many transcription factors. Mapping DNA methylation sites. Identification of histone modification sites Mapping of DNAse sensitive sites•
Goals of ENCODE
_____ influence the growth and function of the gonads
Gonadocorticoids
Histone variants have accumulated mutations that change the amino acid sequence of the histone proteins. All histones have variants that have been identified except for histone _____
H4
_____ DNA has one strand methylated
Hemimethylated
Hypothesis that the pattern of histone modification acts much like a language or code in specifying alterations in chromatin structure
Histone code hypothesis
New methylation (de novo methylation) occurs in both strands Replication of the DNA results in unmethylated daughter strands. This hemimethylated DNA is recognized by DNA methylase, which methylates the unmethylated strand. This process is called maintenance methylation.
How methylation inheritance occurs
Methylated CpG islands inhibit binding of transcription factors Methylation converts chromatin from an open to closed conformation. Methyl-CpG-binding proteins recognize methylated CG sequences and recruit other proteins to the area, compacting the DNA
How methylation inhibits transcription
A NFR is located at the transcriptional start site, where a transcriptional activator binds. Covalent modification of histones by histone acetyltransferases occurs. Modified histones are recognized by DNA-binding proteins that promote changes in the compaction of the chromatin.
How transcriptional activation of a eukaryotic gene may occur
When iron is abundant the iron binds to _____, which causes it to dissociate from the transferrin receptor mRNA and it becomes rapidly degraded
IRP
A segment of DNA that functions as a boundary between two genes
Insulator
Act as a barrier to chromatin-remodeling or histone-modifying enzymes, block the effects of enhancers that exert their effects on neighboring genes, promote the formation of loops that block the effects of nearby enhancers
Insulators
A large protein complex that interacts with RNA polymerase II and various regulatory transcription factors. Depending on its interactions with regulatory transcription factors, mediator may stimulate or inhibit RNA polymerase II
Mediator
_____ may be altered by ATP-dependent chromatin remodeling.
Nucleosome rearrangement
_____ include the ISWI- family, the INO80- family, and the Mi-2-family, and the SWI/SWF family in yeast
Remodeling complexes
_____ is a general transcription factor that binds to the TATA box and is needed to recruit RNA polymerase II to the core promoter
TFIID
Most regulatory transcription factors do not bind directly to the RNA polymerase. Instead, they interact with either _____
TFIID or mediator
Proteins that influence the ability of the RNA polymerase to transcribe a gene are called _____
Transcription factors
Histone acetyltransferases place an acetyl group on positively changed lysine within the core histone proteins. This eliminates the positive charge on the lysine side chain, thereby disrupting the electrostatic attraction between the histone protein and the negatively changed DNA backbone. This leads to _____
a more open chromatin structure
Particular amino acids in the amino-terminal tails of standard histones and histone variants are subject to several types of covalent modifications, including _____
acetylation, methylation, and phosphorylation
A transcription factor that increases the rate of transcription is called an _____, and the DNA sequence it binds to an _____
activator, enhancer
Methylated DNA sequences are inherited during _____
cell division
Chromatin remodeling change chromatin structure by
changing nucleosome position, histone eviction, replacing histones with variants
Some regulatory transcription factors recruit proteins to the promoter, which affects _____
chromatin compaction
_____ refers to the dynamic changes in the structure of chromatin that occur during the life of a cell.
chromatin remodeling
Tightly packed chromatin is said to be in the _____. Chromatin in the open configuration is more accessible to transcription factors and RNA polymerase
closed configuration
When iron levels are high, iron binds to the IRP and causes a _____ that inhibits IRP from binding to IRE. Ferritin mRNA is translated and the ferritin produced stores excess iron.
conformational change
General transcription factors bind the RNA polymerase to the _____
core promoter
CREB proteins are regulatory transcription factors that become activated in response to _____. The response element is called a _____
cyclic-adenosine monophosphate (cAMP), cAMP response element (CRE)
Two glucocorticoid receptors form a _____ and bind to _____ in the nucleus. This activates the transcription of adjacent target genes
dimer, glucocorticoid response elements (GREs)
Steroid hormones are synthesized by _____
endocrine glands (mammals)
A protein call _____ help prevent toxic build up. The two mRNAs that encode ferritin and the transferrin receptor are influenced by an RNA-binding protein called _____. That binds to a regulatory element in the two mRNAs called the _____.
ferritin, iron regulatory protein (IRP), iron response element (IRE)
Regulatory transcription factors regulate the rate of _____
gene transcription
Specialized _____ play specialized roles in chromatin structure and function to create functionally specialized regions of chromatin
histone variants
Two identical transcription factors that come together are called a _____. Two different transcription factors that interact are called a _____.
homodimer, heterodimer
Type of steroid receptor that functions as a regulatory transcription factor where _____ binds. The binding of the hormone releases a protein called HSP90, exposing a _____
hormones, nuclear localization signal (NLS)
In _____ genes, the CpG islands are unmethylated. In _____ genes the CpG islands are methylated
housekeeping, tissue-specific
For active genes or those genes that can be activated, the core promoter is found at a _____. This is typically 150 bp in length
nucleosome-free region (NFR)
Many response elements are _____
orientation-independent, or bidirectional
Most signaling molecules bind to receptors on the _____. This generates an intracellular signal, causing a cellular response. One of these responses may be transcription. Example is CREB
plasma membrane
Transcription factors that decrease the rate of transcription are called _____, and the DNA sequence they bind to is called a _____
repressors, silencer
Regulatory transcription factors that interact with steroid hormones are called _____. Steroid hormones are designed to influence gene expression
steroid receptors
The more tightly wound DNA is upon the histone core, the less accessible it is to other _____
transcription factors
The transferrin receptor mRNA also contains an IRE. When IRP binds to this IRE it prevents the degradation of the mRNA. Therefore when levels of iron are _____, the mRNA can be translated to make more transferrin receptor proteins.
very low