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